U.S. patent application number 10/209591 was filed with the patent office on 2003-02-27 for stent coating.
Invention is credited to Furst, Joseph G..
Application Number | 20030040790 10/209591 |
Document ID | / |
Family ID | 26716476 |
Filed Date | 2003-02-27 |
United States Patent
Application |
20030040790 |
Kind Code |
A1 |
Furst, Joseph G. |
February 27, 2003 |
Stent coating
Abstract
An expandable stent for use within a body passageway having a
body member with two ends and a wall surface disposed between the
ends. The body member has a first diameter to permit delivery of
the body member into a body passageway and a second expanded
diameter. The surface of the stent is coated with a biological
agent and a polymer which controls the release of the biological
agent.
Inventors: |
Furst, Joseph G.;
(Middlefield, OH) |
Correspondence
Address: |
FAY, SHARPE, FAGAN, MINNICH & McKEE
Seventh Floor
1100 Superior Avenue
Cleveland
OH
44114-2579
US
|
Family ID: |
26716476 |
Appl. No.: |
10/209591 |
Filed: |
July 31, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10209591 |
Jul 31, 2002 |
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10039816 |
Oct 26, 2001 |
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10039816 |
Oct 26, 2001 |
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09771073 |
Jan 29, 2001 |
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09771073 |
Jan 29, 2001 |
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09273736 |
Mar 22, 1999 |
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6436133 |
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60081824 |
Apr 15, 1998 |
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60094250 |
Jul 27, 1998 |
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Current U.S.
Class: |
623/1.11 |
Current CPC
Class: |
A61F 2250/0098 20130101;
Y02A 50/30 20180101; A61L 31/16 20130101; A61F 2002/91533 20130101;
A61F 2/91 20130101; A61F 2310/0097 20130101; A61F 2230/0054
20130101; A61F 2/915 20130101; A61L 2300/426 20130101; A61F
2002/91566 20130101; A61F 2250/0068 20130101; A61L 31/10 20130101;
A61L 2300/602 20130101; A61L 2300/42 20130101; A61F 2002/91575
20130101; A61K 9/0024 20130101; A61L 2300/606 20130101 |
Class at
Publication: |
623/1.11 |
International
Class: |
A61F 002/06 |
Claims
What is claimed is:
1. An expandable stent for use within in a body passageway
including a body member, a intermediate compound, and a biological
agent, said body member having first and second ends and a wall
surface disposed between said first and second ends defining a
longitudinal axis of said body member, said body member having a
first cross-sectional shape having a first cross-sectional area
which permits intraluminal delivery of said body member into the
body cavity, and a second expanded cross-sectional shape having a
second cross-sectional area which is greater than said first
cross-sectional area, said biological agent at least partially
coated on the surface of said body member, said intermediate
compound at least partially securing said biological agent to said
body member, said intermediate compound including at least one
radiation induced cross-linking that at least partially
encapsulates at least a portion of said biological agent in said
intermediate compound.
2. The stent as defined in claim 1, wherein said biological agent
is releasably coated on said stent.
3. The stent as defined in claim 1, wherein said cross-linking in
said intermediate compound at least partially delays delivery of
said biological agent into said body passageway.
4. The stent as defined in claim 2, wherein said cross-linking in
said intermediate compound at least partially delays delivery of
said biological agent into said body passageway.
5. The stent as defined in claim 1, wherein at least a portion of
said biological agent forms a polymer salt complex with said
intermediate compound.
6. The stent as defined in claim 4, wherein at least a portion of
said biological agent forms a polymer salt complex with said
intermediate compound.
7. The stent as defined in claim 1, wherein said intermediate
compound includes a polymer, a copolymer or mixtures thereof.
8. The stent as defined in claim 6, wherein said intermediate
compound includes a polymer, a copolymer or mixtures thereof.
9. The stent as defined in claim 1, wherein said intermediate
compound includes hydrophobic and hydrophilic compounds.
10. The stent as defined in claim 8, wherein said intermediate
compound includes hydrophobic and hydrophilic compounds.
11. The stent as defined in claim 1, wherein said intermediate
compound includes an ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
12. The stent as defined in claim 11, wherein said intermediate
compound includes an ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
13. The stent as defined in claim 8, wherein said intermediate
compound includes an ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
14. The stent as defined in claim 1, wherein said biological agent
includes Trapidil, GM-CSF, and mixtures thereof.
15. The stent as defined in claim 13, wherein said biological agent
includes Trapidil, GM-CSF, and mixtures thereof.
16. The stent as defined in claim 1, wherein said wall surface
being at least partially formed by a plurality of intersecting
elongated members, at least some of said elongated members
intersecting with one another intermediate said first and second
ends of said body member, said plurality of intersecting elongated
members forming a plurality of openings in said wall surface, at
least one of said openings in said wall surface is formed of at
least four intersecting elongated members which define the top,
bottom and two sides of said opening, said top and said bottom
sides are substantially parallel to one another in said first and
said second cross-sectional shapes of said body member.
17. The stent as defined in claim 15, wherein said wall surface
being at least partially formed by a plurality of intersecting
elongated members, at least some of said elongated members
intersecting with one another intermediate said first and second
ends of said body member, said plurality of intersecting elongated
members forming a plurality of openings in said wall surface, at
least one of said openings in said wall surface is formed of at
least four intersecting elongated members which define the top,
bottom and two sides of said opening, said top and said bottom
sides are substantially parallel to one another in said first and
said second cross-sectional shapes of said body member.
18. The expandable intraluminal graft as defined in claim 16,
wherein said top and bottom sides of said opening are substantially
parallel along said longitudinal axis of said body member.
19. The expandable intraluminal graft as defined in claim 17,
wherein said top and bottom sides of said opening are substantially
parallel along said longitudinal axis of said body member.
20. The expandable intraluminal graft as defined in claim 16,
wherein said two sides of said opening are substantially parallel
to one another in said first and said second cross-sectional shapes
of said body member.
21. The expandable intraluminal graft as defined in claim 18,
wherein said two sides of said opening are substantially parallel
to one another in said first and said second cross-sectional shapes
of said body member.
22. The expandable intraluminal graft as defined in claim 19,
wherein said two sides of said opening are substantially parallel
to one another in said first and said second cross-sectional shapes
of said body member.
23. The expandable intraluminal graft as defined in claim 16,
wherein at least one of said openings in said wall surface having a
substantially parallelogram shape when said body member is in said
first cross-sectional shape.
24. The expandable intraluminal graft as defined in claim 21,
wherein at least one of said openings in said wall surface having a
substantially parallelogram shape when said body member is in said
first cross-sectional shape.
25. The expandable intraluminal graft as defined in claim 22,
wherein at least one of said openings in said wall surface having a
substantially parallelogram shape when said body member is in said
first cross-sectional shape.
26. The stent as defined in claim 1, wherein said wall surface
including a first and second set of slots about a circumference of
said body member, each set of slots including at least two slots
positioned substantially parallel to one another along said
longitudinal axis of said body member, said first and said second
set of slots forming an angle between said sets of slots between
0-90.degree. when said body member is in said first cross-sectional
shape.
27. The stent as defined in claim 15, wherein said wall surface
including a first and second set of slots about a circumference of
said body member, each set of slots including at least two slots
positioned substantially parallel to one another along said
longitudinal axis of said body member, said first and said second
set of slots forming an angle between said sets of slots between
0-90.degree. when said body member is in said first cross-sectional
shape.
28. The expandable intraluminal graft as defined in claim 26,
wherein a plurality of said slots of said one set of slots include
first and second ends, at least two adjacently positioned slots
having said first and said second ends, said first ends of said
slots lying in a first plane substantially parallel to a
longitudinal axis of said body member when said body member is in
said first cross-sectional shape, said second ends of said slots
lying in a second plane substantially parallel to a longitudinal
axis of said body member when said body member is in said first
cross-sectional shape, said first and second set of slots are not
parallel to said longitudinal axis of said body member when said
body member is in said first cross-sectional shape.
29. The expandable intraluminal graft as defined in claim 27,
wherein a plurality of said slots of said one set of slots include
first and second ends, at least two adjacently positioned slots
having said first and said second ends, said first ends of said
slots lying in a first plane substantially parallel to a
longitudinal axis of said body member when said body member is in
said first cross-sectional shape, said second ends of said slots
lying in a second plane substantially parallel to a longitudinal
axis of said body member when said body member is in said first
cross-sectional shape, said first and second set of slots are not
parallel to said longitudinal axis of said body member when said
body member is in said first cross-sectional shape.
30. The expandable intraluminal graft as defined in claim 26,
wherein a plurality of said slots of said one set of slots include
first and second ends, at least two adjacently positioned slots
having said first and said second ends, said first ends of said
slots lying in a first plane substantially parallel to a
longitudinal axis of said body member when said body member is in
said second cross-sectional shape, said second ends of said slots
lying in a second plane substantially parallel to a longitudinal
axis of said body member when said body member is in said second
cross-sectional shape.
31. The expandable intraluminal graft as defined in claim 29,
wherein a plurality of said slots of said one set of slots include
first and second ends, at least two adjacently positioned slots
having said first and said second ends, said first ends of said
slots lying in a first plane substantially parallel to a
longitudinal axis of said body member when said body member is in
said second cross-sectional shape, said second ends of said slots
lying in a second plane substantially parallel to a longitudinal
axis of said body member when said body member is in said second
cross-sectional shape.
32. The expandable intraluminal graft as defined in claim 26,
wherein said first and second set of slots are not parallel to said
longitudinal length of said body member when said body member is in
said second cross-sectional shape.
33. The expandable intraluminal graft as defined in claim 31,
wherein said first and second set of slots are not parallel to said
longitudinal length of said body member when said body member is in
said second cross-sectional shape.
34. The expandable intraluminal graft as defined in claim 26,
wherein said body member is formed from a single piece of
material.
35. The expandable intraluminal graft as defined in claim 33,
wherein said body member is formed from a single piece of
material.
36. The expandable intraluminal graft as defined in claim 1,
wherein said body member maintains a substantially constant
longitudinal length when expanded from said first cross-sectional
shape to said second cross-sectional shape.
37. The expandable intraluminal graft as defined in claim 25,
wherein said body member maintains a substantially constant
longitudinal length when expanded from said first cross-sectional
shape to said second cross-sectional shape.
38. The expandable intraluminal graft as defined in claim 35,
wherein said body member maintains a substantially constant
longitudinal length when expanded from said first cross-sectional
shape to said second cross-sectional shape.
39. The expandable intraluminal graft as defined in claim 1,
wherein said graft includes two body members and at least one
connector connected between said two body members, said connector
allowing transverse bending flexibility invariant to the plane of
bending of said graft.
40. The expandable intraluminal graft as defined in claim 37,
wherein said graft includes two body members and at least one
connector connected between said two body members, said connector
allowing transverse bending flexibility invariant to the plane of
bending of said graft.
41. The expandable intraluminal graft as defined in claim 39,
wherein said graft includes two body members and at least one
connector connected between said two body members, said connector
allowing transverse bending flexibility invariant to the plane of
bending of said graft.
42. The expandable intraluminal graft as defined in claim 39,
wherein said connector is substantially "U" shaped or "V"
shaped.
43. The expandable intraluminal graft as defined in claim 1,
wherein said body member is substantially tubular.
44. The expandable intraluminal graft as defined in claim 1,
wherein said second cross-sectional area of said body member is
variable.
45. The expandable intraluminal graft as defined in claim 1,
wherein said first and second ends having a substantially smooth
surface.
46. The expandable intraluminal graft as defined in claim 40,
wherein said first and second ends having a substantially smooth
surface.
47. The expandable intraluminal graft as defined in claim 41,
wherein said first and second ends having a substantially smooth
surface.
48. The expandable intraluminal graft as defined in claim 1,
wherein a plurality of said intersecting elongated members are at
least partially formed by a process including etching, laser
cutting, and combinations thereof.
49. The expandable intraluminal graft as defined in claim 1,
wherein said body member is at least partially coated with a
material that is visible under fluoroscopy, said material being
coated on an outer surface of said body member and at least one end
of said body member.
50. The expandable intraluminal graft as defined in claim 1,
wherein said body member is treated with Gamma or Beta radiation to
reduce the vascular narrowing of at least a portion of said body
cavity.
51. The expandable intraluminal graft as defined in claim 1,
including a balloon, said balloon including at least one opening to
allow delivery of said biological substance from an interior of
said balloon to said body cavity, said biological substance
includes said biological agent.
52. A biological matrix comprising a base compound and biological
agent, said base compound including a polymer, copolymer or
mixtures thereof, said base compound at least partially
encapsulating at least a portion of said biological agent, said
base compound including at least one radiation induced
cross-linking, said at least one radiation induced cross-linking at
least partially entrapping said biological agent in said base
compound.
53. The biological matrix as defined in claim 52, wherein at least
a portion of said biological agent forms a polymer salt complex
with said base compound.
54. The biological matrix as defined in claim 52, wherein said base
compound includes hydrophobic and hydrophilic compounds.
55. The biological matrix as defined in claim 53, wherein said base
compound includes hydrophobic and hydrophilic compounds.
56. The biological matrix as defined in claim 52, wherein said base
compound includes ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
57. The biological matrix as defined in claim 54, wherein said base
compound includes ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
58. The biological matrix as defined in claim 55, wherein base
compound includes ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
59. The biological matrix as defined in claim 52, wherein said
biological agent includes Trapidil and GM-CSF.
60. A method for producing an expandable stent coated with a
biological agent comprising: a) selecting a stent having a body
member, said body member having a first cross-sectional shape
having a first cross-sectional area which permits intraluminal
delivery of said body member into the body cavity, and a second
expanded cross-sectional shape having a second cross-sectional area
which is greater than said first cross-sectional area; b) coating
at least a portion of said body member with a mixture of an
intermediate compound and a biological agent, said intermediate
compound including polymer, copolymer and combinations thereof;
and, c) applying radiation to said coating to cause at least one
cross-link to form in said intermediate compound that at least
partially encapsulates at least a portion of said biological agent
in said intermediate compound.
61. The method as defined in claim 60, wherein said intermediate
compound includes ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
62. The method as defined in claim 60, wherein said biological
agent includes Trapidil, GM-CSF, and mixtures thereof.
63. The method as defined in claim 61, wherein said biological
agent includes Trapidil, GM-CSF, and mixtures thereof.
64. A method for producing an expandable stent coated with a
biological agent comprising: a) selecting a stent having a body
member, said body member having a first cross-sectional shape
having a first cross-sectional area which permits intraluminal
delivery of said body member into the body cavity, and a second
expanded cross-sectional shape having a second cross-sectional area
which is greater than said first cross-sectional area; b) coating
at least a portion of said body member with a mixture of an
intermediate compound and a biological agent, said intermediate
compound including polymer, copolymer and combinations thereof;
and, c) applying radiation to said coating to cause at least one
salt complex to form between intermediate compound and said
biological agent.
65. The method as defined in claim 64, wherein said intermediate
compound includes ethylene-acrylic acid copolymer, parylene,
parylene derivatives, and mixtures thereof.
66. The method as defined in claim 64, wherein said biological
agent includes Trapidil, GM-CSF, and mixtures thereof.
67. The method as defined in claim 65, wherein said biological
agent includes Trapidil, GM-CSF, and mixtures thereof.
Description
[0001] The present application is a continuation-in-part of
co-pending U.S. patent application Ser. No. 10/039,816 filed Oct.
26, 2001 entitled "Irradiated Stent Coating", which in turn is a
continuation-in-part of co-pending U.S. patent application Ser. No.
09/771,073 filed Jan. 29, 2001 entitled "Improved Expandable
Graft", which in turn is a continuation-in-part of co-pending U.S.
patent application Ser. No. 09/273,736 filed Mar. 22, 1999 entitled
"Improved Expandable Graft", which in turn claims priority on U.S.
Provisional Patent Application Serial No. 60/081,824 filed Apr. 15,
1998. The present application is also a continuation-in-part of
co-pending U.S. patent application Ser. No. 10/039,816 filed Oct.
26, 2001 entitled "Irradiated Stent Coating", which in turn is a
continuation-in-part of co-pending U.S. patent application Ser. No.
09/771,073 filed Jan. 29, 2001 entitled "Improved Expandable
Graft", which in turn is a continuation-in-part of U.S. patent
application Ser. No. 09/363,052 filed Jul. 29, 1999 entitled
"Coated Intraluminal Graft", now U.S. Pat. No. 6,206,916, which in
turn claims priority on U.S. Provisional Patent Application Serial
No. 60/094,250 filed Jul. 27, 1998.
[0002] This invention relates to an implant for use within a body
and, more particularly, an expandable stent which is particularly
useful for repairing various types of body passageways, and even
more particularly to an expandable stent that includes and/or is at
least partially coated and/or a impregnated with one or more
biological agents which stent and one or more biological agents are
useful in repairing blood vessels narrowed or occluded by disease.
Although the present invention is particularly applicable to
stents, the biological agent delivery system of the present
invention can be used in conjunction with various types of implants
such as, but not limited to, prosthetic devices. As such, the
biological agent delivery system can form one or more components of
other types of implants and/or be coated and/or impregnated onto at
least a portion of other types of implants to deliver one or more
biological agent to a particular site. Furthermore, the biological
agent delivery system can be used in conjunction with, or used
separate from, a stent and/or other types of implants to deliver a
biological agent into a body cavity, organ or other part of the
body. In addition, the present invention is particularly directed
for use in humans; however, the present invention can be used in
animals and some types of plants.
INCORPORATION BY REFERENCE
[0003] U.S. Pat. Nos. 4,733,665; 4,739,762; 5,195,984; 5,725,572;
5,735,871; 5,755,781; 5,853,419; 5,861,027; 6,007,573; 6,059,810;
6,099,561; 6,200,337; 6,206,916; and 6,379,379; and U.S. patent
application Ser. Nos. 09/273,736 filed Mar. 22, 1999; 09/771,073
filed Jan. 29, 2001; and 10/039,816 filed Oct. 26, 2001; and PCT
Patent Application No. WO 99/56663 are incorporated herein by
reference to illustrate various types and configurations of stents,
the process or method of manufacturing stents, and the method by
which such stents are used. U.S. Pat. Nos. 5,102,417; 5,355,832;
5,447,799; 5,464,650; 5,578,075; 5,616,608; 5,679,400; 5,716,981;
5,733,925; 5,916,585; 5,981,568; 6,120,847; 6,156,373; 6,206,916;
6,258,121; 6,273,913; 6,287,628; 6,299,604; 6,306,421; 6,322,847;
6,368,658; and 6,379,379; U.S. patent application Ser. Nos.
09/273,736 filed Mar. 22, 1999; 09/771,073 filed Jan. 29, 2001; and
10/039,816 filed Oct. 26, 2001; and PCT Patent Application Nos. WO
90/13332; WO 91/12779; WO 99/56663; and WO 01/17577 are
incorporated herein by reference to illustrate various biological
agents that can be coated onto stents, coating compositions that
can be used to coat various biological agents onto stents, and/or
coating techniques used to coat coatings onto stents. The disclosed
biological agents are merely a few examples of the biological
agents that can be used in the present invention.
BACKGROUND OF THE INVENTION
[0004] Heart disease is still one of the most prevalent medical
ailments in the world. Intraluminal endovascular grafting, a type
of angioplasty procedure, has been demonstrated by experimentation
to present a possible alternative to conventional vascular surgery
and is used to treat heart disease. Intraluminal endovascular
grafting involves a tubular prosthetic graft or stent and delivery
within the vascular system. As defined herein, the terms "graft"
and "stent" are used interchangeably. Advantages of this method
over conventional vascular surgery include obviating the need for
surgically exposing, incising, removing, replacing, or bypassing
the defective blood vessel. Over 20 million angioplasty or related
procedures involving occluded vasculature have been preformed
worldwide. About 30% of these angioplasties fail within 30 days.
These failures typically require the procedure to be repeated.
[0005] Several years ago, a product called a stent, named after
Charles Stent, was introduced for use in angioplasty procedures.
The stent reduced the angioplasty failure rate to about 15 percent.
A stent is an expandable metal tubular device that is mounted over
an angioplasty balloon and deployed at the site of coronary
narrowing. The balloon is inflated to expand the stent to
physically open and return patency to the body passageway. After
the stent is expanded, the balloon is deflated and removed and the
stent is permanently disposed to retain the opened body passageway.
The first generation of expandable stents did not offer a
controllable radial expansion. An improved stent disclosed in U.S.
Pat. No. 4,733,665 overcame the problem associated with controlled
stent expansion. However, prior art stents still do not provide
control over the final, expanded configuration of the stent. For
instance, the expansion of a particular coiled, spring-type stent
is predetermined by the method of manufacture, material, and/or
delivery system. In the case of self-expanding intraluminal stents
formed of a heat sensitive material which expands upon exposure to
core body temperature, the amount of expansion is predetermined by
the heat expansion properties of the particular alloy utilized in
the manufacture of the intraluminal stent. Consequently, once the
foregoing types of intraluminal stents were expanded at the desired
location within a body passageway, the expanded size of the stent
could not be increased. If the proposed expanded diameter of the
narrow body passageway was not determined correctly, the stent
might not expand enough to contact the interior surface of the body
passageway so as to be secured thereto and/or not expand the body
passageway to the desired diameter. The stent disclosed in the '665
patent overcame the problems associated with these past stent
designs.
[0006] The stent based upon the '665 patent is currently being used
in angioplasty procedures. Stents, including the stent of the '665
patent, are presently used in approximately 30-60 percent of all
angioplasty procedures. However, these stents have several
shortcomings which contribute to procedural failure rates. The
currently used stents are not readily visible under fluoroscopic
guidance procedures. Stent placement is hindered as a result of
poor visibility. As a result, precise positioning of the stent
during the insertion procedure was difficult to achieve.
Consequently, the stent could be inadvertently positioned in the
wrong or non-optimal location in the body passageway. These stents
also shorten longitudinally after radial expansion, which is not
desirable for their intended use. The shortening of the stent
resulted in longitudinal movement of the stent during expansion,
which sometimes resulted in the stent being fully expanded in the
wrong or non-optimal position. One stent design was proposed in
U.S. Pat. No. 5,853,419. The stent included a hexagon in the side
wall of the stent which theoretically resulted in the stent
retaining its longitudinal length during expansion. The stent also
included ends that flared outwardly. However, in practice, the
stent does not expand as described in the '419 patent. Due to the
hexagonal configuration of the openings in the stent, the struts
that form the hexagonal configuration cause the ribs of the
hexagonal configuration to bend, buckle or twist when the struts
are being expanded, thus resulting in a reduction in the
longitudinal length of the stent. The bending, buckling or twisting
of the ribs can only be avoided if the struts are made of a very
flexible or bendable material; however, the use of such material
compromises the strength of the stent. Not only does the stent not
retain its longitudinal length, the complex stent design is both
difficult to manufacture and to uniformly expand in a body
passageway.
[0007] The improved stent disclosed in U.S. patent application Ser.
No. 09/273,736 filed Mar. 22, 1999, which is incorporated herein by
reference, overcomes these past problems with stents. The patent
application discloses an improved stent that can be coated with one
or more substances in various regions of the stent to improve the
visibility of the stent by various techniques (e.g. fluoroscopy)
during the insertion procedure, thereby improving the positional
accuracy of the stent in the body passageway. The improved stent
also incorporates a unique design which enables the stent to retain
its original longitudinal length during expansion. The improved
stent also is easier to manufacture and substantially uniformly
expands in the body passageway.
[0008] Although the improved stent overcomes the deficiencies of
prior art stents with respect to accurate stent positioning,
problems can still exist with respect to tissue damage by the stent
during insertion and/or expansion of the stent. The two ends of
prior art stents typically include one or more rough, sharp and/or
pointed surfaces. These surfaces can cause irritation and/or damage
to surrounding tissue as the stent is moved within the body
passageways. Such irritation or damage to the surrounding tissue
can create various types of complications during the surgical
procedure. These surfaces can also cause damage to surrounding
tissue during the expansion of the stent. During stent expansion,
the middle of the stent is first expanded by the angioplasty
balloon. As the middle of the stent expands, the ends of the stent
move toward one another. This movement of the ends can result in
the stent ends digging into and/or penetrating the surrounding
tissue. Furthermore, tissue damage can result when the end portions
of the stent are eventually expanded by the angioplasty balloon.
Stent designs that have flared out ends can also cause damage to
tissue during insertion of the stent and expansion of the stent.
U.S. patent application Ser. No. 09/771,073 filed Jan. 29, 2001,
which is incorporated herein by reference, includes a stent design
that overcomes or minimizes tissue damage by the stent during stent
insertion and stent expansion. The stent includes rounded and/or
smooth edges for the end portions of the stent.
[0009] Several problems can develop after the stent is inserted
into a body passageway. One problem is known as in-stent restenosis
wherein the body passageway, which has been previously treated with
a stent, renarrows or closes within the stented segment. The
renarrowing or closure of the body passageway can be caused by a
structural failure of the stent due to contractive forces by the
body passageway on the stent and/or by the body passageway growing
into the openings in the stent. Other problems can include vascular
narrowing and restenosis. Vascular narrowing is defined as a
vascular segment that has not been previously treated by any
interventional means and eventually closes, thereby preventing a
fluid body passageway. Restenosis is the renarrowing of a
previously treated vascular segment not involving a stent. Both of
these problems are the result of a body passageway that was not
treated with an invasive angioplasty, narrowing or closing, and
from the insertion of a stent in one portion of the body passageway
causing vascular narrowing or restenosis in another part of the
body passageway. Vascular narrowing, restenosis and in-stent
restenosis are caused by biological factors causing the premature
closing of the body passageways. One such biological factor is
platelet derived growth factor, referred to as PDGF. PDGF is an
intercellular messenger capable of stimulating proliferation of
smooth muscle cells. Smooth muscle cells are known to migrate
within body passageways such as arteries and cause a restenotic
reaction.
[0010] The problems with vascular narrowing, restenosis and
in-stent restenosis are significantly overcome by the use of one or
more drugs. U.S. Pat. No. 6,206,916 entitled "Coated Intraluminal
Graft," which is incorporated herein by reference, discloses the
use of a drug coated on at least a portion of the stent to inhibit
or prevent the occurrence of in-stent restenosis, vascular
narrowing and/or restenosis. Although the intravenous use of drugs
and/or the coating of the stent with drugs can inhibit or prevent
the occurrence of in-stent restenosis, vascular narrowing and/or
restenosis, the continued need for the drugs after the stent has
been inserted can require the patient to be retained in the
hospital for extended periods of time. Furthermore, in-stent
restenosis, vascular narrowing and/or restenosis may occur days or
weeks after the stent insertion procedure and after intravenous use
of drugs has terminated and/or the drug coating on the stent has
been dissolved off the stent. Several other United States patents
disclose the use of various drugs coated on stents. For example,
U.S. Pat. No. 5,716,981, which is incorporated herein by reference,
discloses the use of paclitaxel or an analog or derivative thereof
for use on a stent. U.S. Pat. Nos. 5,733,925 and 5,981,568, which
are incorporated herein by reference, disclose the use of taxol or
a water soluble taxol derivative; cytochalasin or analog thereof;
or other type of cytoskeletal inhibitor for use on a stent. Several
United States patents also disclose the use of polymers to bind the
various drugs to the surface of the stent. Several of these
polymers are disclosed in U.S. Pat. Nos. 5,578,075 and 5,679,400,
which are incorporated herein by reference. U.S. Pat. No.
5,464,650, which is incorporated herein by reference, discloses the
method of applying several coatings of a polymer that has been
mixed with a drug so as to control the delivery of the drug in a
body over a period of time. The method of coating the stent
involves a series of steps that significantly increases the cost,
complexity and time for the manufacture of the stent.
[0011] In view of the present stent technology, there is a need and
demand for a stent that has improved procedural success rates, has
higher visibility under fluoroscopy in vivo, retains its
longitudinal dimensions from its original pre-expanded
configuration to its expanded configuration, minimizes damage to
tissue during insertion and expansion of the stent, inhibits or
prevents the occurrence of in-stent restenosis, vascular narrowing
and/or restenosis long after the stent has been inserted into a
body passageway, and is simple and cost effective to
manufacture.
SUMMARY OF THE INVENTION
[0012] This invention pertains to an improved expandable stent
designed to meet the present day needs and demands relating to
stents. The present invention is directed to a stent and will be
particularly described with respect thereto; however, the present
invention has much broader scope and can be applied in part to a
wide variety of implants (e.g., prosthetic implants, heart pacers,
organ implants, and/or other electronic and/or mechanical
implants). The stent has a body member that includes first and
second ends and a wall surface disposed between the first and
second ends. The wall surface is typically formed by a plurality of
intersecting elongated members, and at least some of the elongated
members typically intersect with one another at a point
intermediate to the first and second ends of the body member.
Alternatively, or in addition, the wall surface includes one or
more slots. The body member has a first cross-sectional area which
permits delivery of the body member into a body passageway, and a
second, expanded cross-sectional area. As defined herein, the term
"body passageway" means any passageway or cavity in a living
organism, including humans, animals and plants. A "body passageway"
in an animal or human includes, but is not limited to, the bile
duct, bronchiole tubes, nasal cavity, blood vessels, heart,
esophagus, trachea, stomach, fallopian tube, uterus, ureter,
urethra, the intestines, lymphatic vessels, nasal passageways,
eustachian tube, acoustic meatus, and/or the like. The invention
when used in association with stents is particularly applicable for
use in blood vessels, and will hereinafter be particularly
described with reference thereto. The expansion of the stent body
member can be accomplished in a variety of manners. Typically, the
body member is expanded to its second cross-sectional area by a
radially, outwardly extending force applied at least partially from
the interior region of the body member. Alternatively or
additionally, the body member can include heat sensitive materials
that expand upon exposure to heat. The second cross-sectional area
of the stent can be fixed or variable. When the second
cross-sectional area is variable, the second cross-sectional area
is typically dependent upon the amount of radially outward force
applied to the body member. Generally, the body member is expanded
so as to expand at least a portion of the body passageway while
retaining the original length of the body member. In one particular
body member design, the first cross-sectional shape of the body
member is substantially uniformly circular so as to form a
substantially tubular body member; however, the body member can
have other cross-sectional shapes such as, but not limited to,
elliptical, oval, polygonal, trapezoidal, and the like. As can be
appreciated, the cross-sectional shape of the body member can be
uniform or non-uniform in the first and/or second cross-sectional
shape. In addition, if more than one body member is included in a
stent, all the body members can have substantially the same size
and shape, or one or more of the body members can have a different
size and/or shape from one or more other body members.
[0013] Another and/or alternative feature of the present invention
is that the stent includes a plurality of elongated members wherein
one or more elongated members is a wire. In one embodiment of the
present invention, the elongated members include a plurality of
wires wherein the two or more of the wires are secured to one
another where a plurality of wires intersect with one another. Two
or more of the wires can be connected together by a variety of
techniques such as, but not limited to, welding, soldering,
brazing, adhesives, lock and groove configurations, snap
configurations, melting together the wires, and the like. In
another and/or alternative embodiment of the present invention, the
body member is at least partially in the form of a wire mesh
arrangement. In one aspect of this embodiment, the wire mesh
arrangement is utilized as the stent. In another and/or alternative
aspect of this embodiment, the wire mesh arrangement is designed to
be expanded to a second diameter within the body passageway. In one
non-limiting design, the second expanded diameter is variable and
determined by the desired expanded internal diameter of the body
passageway. In another and/or alternative design, the second
expanded diameter is selected so that the expanded wire mesh
arrangement will not or substantially not migrate from the desired
location within the body passageway. In still another and/or
alternative non-limiting design, the expansion of the stent does
not or substantially does not cause a rupture of the body
passageway. In still another and/or alternative embodiment of the
present invention, the plurality of wires forms a plurality of
polygonal shaped regions on the body of the stent. In one aspect of
this embodiment, the polygonal regions are aligned along the
longitudinal axis of the body of the stent. In another and/or
alternative aspect of this embodiment, the body of the stent
includes a plurality of polygonal regions that are aligned along
the longitudinal axis and lateral axis of the stent body. In one
non-limiting design, the plurality of polygonal regions aligned
along the longitudinal axis of the stent body are oriented
substantially the same with respect to one another, and the
plurality of polygonal regions aligned along the lateral axis are
oriented differently from one another. In another and/or
alternative non-limiting design, the polygonal regions that are
aligned along the same longitudinal axis have a top that lies in
the same longitudinal axis and have a bottom that lies in the same
longitudinal axis, and the polygonal regions that are aligned along
the same latitudinal axis have sides that do not lie in the same
latitudinal axis; however, alternating polygonal regions have sides
that are substantially parallel to one another. In still another
and/or alternative non-limiting design, the side wall of at least
one body member includes an even number of polygonal regions about
the peripheral surface of the body member. In yet another and/or
alternative embodiment of the present invention, the polygonal
shape, upon expansion, retains the original longitudinal length of
the body of the stent. In one aspect of this embodiment, a
plurality of polygonal shapes have a substantially parallelogram
shape. In another and/or alternative aspect of this embodiment, the
body member includes about 2-15 polygonal shapes along the
longitudinal length of the body member, typically about 2-10
polygonal shapes, and more typically about 2-8 polygonal shapes;
however, more polygonal shapes can be used depending on the shape
and/or size of the body member.
[0014] Yet another and/or alternative feature of the present
invention is that the stent includes a plurality of elongated
members wherein one or more elongated members is a thin bar. In one
embodiment of the present invention, the elongated members include
a plurality of thin bars wherein two or more of the thin bars are
secured to one another where a plurality of bars intersect with one
another. Two or more of the thin bars can be connected together by
a variety of techniques such as, but not limited to, welding,
soldering, brazing, adhesives, lock and groove configurations, snap
configurations, melting together the thin bars, and the like. In
still another and/or alternative embodiment of the present
invention, the plurality of thin bars forms a plurality of
polygonal shaped regions on the body of the stent. In one aspect of
this embodiment, the polygonal regions are aligned along the
longitudinal axis of the body of the stent. In another and/or
alternative aspect of this embodiment, the body of the stent
includes a plurality of polygonal regions that are aligned along
the longitudinal axis and lateral axis of the stent body. In one
non-limiting design, the plurality of polygonal regions aligned
along the longitudinal axis of the stent body are oriented
substantially the same with respect to one another, and the
plurality of polygonal regions aligned along the lateral axis are
oriented differently from one another. In another and/or
alternative non-limiting design, the polygonal regions that are
aligned along the same longitudinal axis have a top that lies in
the same longitudinal axis and have a bottom that lies in the same
longitudinal axis, and the polygonal regions that are aligned along
the same latitudinal axis have sides that do not lie in the same
latitudinal axis; however, alternating polygonal regions have sides
that are substantially parallel to one another. In still another
and/or alternative aspect of this embodiment, the side wall of at
least one body member includes an even number of polygonal regions
about the peripheral surface of the body member. In yet another
and/or alternative embodiment of the present invention, the
polygonal shape, upon expansion, substantially retains the original
longitudinal length of the body of the stent. In one aspect of this
embodiment, a plurality of polygonal shapes have a substantially
parallelogram shape. In another and/or alternative aspect of this
embodiment, the body member includes about 2-15 polygonal shapes
along the longitudinal length of the body member, typically about
2-10 polygonal shapes, and more typically about 2-8 polygonal
shapes; however, more polygonal shapes can be used depending on the
shape and/or size of the body member.
[0015] Still yet another and/or alternative feature of the present
invention is that the side wall of at least one body member of the
stent includes a plurality of elongated members that are arranged
to form at least one polygonal shape. In one embodiment of the
present invention, the polygonal shape, upon expansion, retains the
original longitudinal length of the body of the stent. In one
aspect of this embodiment, a plurality of polygonal shapes have a
substantially parallelogram shape. In another and/or alternative
aspect of this embodiment, the body member of the stent is formed
from a flat piece of material. On the surface of the flat material
there are formed a plurality of polygonal shaped regions. The flat
material is rolled or otherwise formed and the side edges of the
flat material are connected together to form the stent. The side
edges of the flat material can be connected together by a variety
of techniques such as, but not limited to, welding, soldering,
brazing, adhesives, lock and groove configurations, snap
configurations, melting together the edges, and the like. The
polygonal regions in the flat material can also be formed by a
variety of techniques such as, but not limited to, mechanical
cutting, laser cutting, etching, molding, stamping, and/or the
like. In one non-limiting design, the polygonal regions are aligned
along the longitudinal axis of the flat material. In another and/or
alternative non-limiting design, the flat material includes a
plurality of polygonal regions aligned along the longitudinal axis
and lateral axis of the flat material. In still another and/or
alternative non-limiting design, the plurality of polygonal regions
aligned along the longitudinal axis of the flat material are
oriented substantially the same with respect to one another, and
the plurality of polygonal regions aligned along the lateral axis
are oriented differently from one another. In yet another and/or
alternative non-limiting design, the polygonal regions that are
aligned along the same longitudinal axis have a top that lies in
the same longitudinal axis and have a bottom that lies in the same
longitudinal axis, and the polygonal regions that are aligned along
the same latitudinal axis have sides that do not lie in the same
latitudinal axis; however, alternating polygonal regions have sides
that are substantially parallel to one another. In still yet
another and/or alternative non-limiting design, the side wall of at
least one body member includes an even number of polygonal regions
about the peripheral surface of the body member. In a further
and/or alternative non-limiting design, the body member includes
about 2-15 polygonal shapes along the longitudinal length of the
body member, typically about 2-10 polygonal shapes, and more
typically about 2-8 polygonal shapes; however, more polygonal
shapes can be used depending on the shape and/or size of the body
member.
[0016] Another and/or alternative feature of the present invention
is that the side wall of at least one body member of the stent
includes at least one set of slots. In one embodiment of the
present invention, the one or more sets of slots are arranged to
substantially maintain the original longitudinal length of the body
member when the body member is expanded. In one aspect of this
embodiment, the body member of the stent is formed from a
substantially flat single piece of material. On the surface of the
flat material there is formed a plurality of slots. The flat
material is rolled or otherwise formed and the side edges of the
flat material are connected together to form the stent. The side
edges of the flat material can be connected together by a variety
of techniques such as, but not limited to, welding, soldering,
brazing, adhesives, lock and groove configurations, snap
configurations, melting together the edges, and the like. The slots
in the flat material can also be formed by a variety of techniques
such as, but not limited to, mechanical cutting, laser cutting,
etching, molding, stamping, and/or the like. In another and/or
alternative embodiment of the present invention, at least one set
of slots forms substantially a V-shape when the body member is
unexpanded. In one aspect of this embodiment, body portion includes
a plurality of V-shapes. In one non-limiting design of this aspect,
a plurality of V-shapes are aligned along the longitudinal axis of
the side wall of the body member and are positioned in a partial
stacked position with respect to one another to form a set of
V-shapes. Generally, the body member includes about 2-20 V-shapes
in each set of V-shapes, typically about 2-10 V-shapes, and more
typically about 2-5 V-shapes; however, more V-shapes per set can be
used depending on the shape and/or size of the body member. In
another and/or alternative non-limiting design, a plurality of
V-shapes are aligned along the latitudinal axis of the side wall of
the body member. In still another and/or alternative non-limiting
design, at least a plurality of the V-shapes are substantially
equally spaced from one another. In yet another and/or alternative
non-limiting design, an even number of V-shapes are aligned along
the latitudinal axis of the side wall of the body member. In still
yet another and/or alternative non-limiting design, at least a
plurality of V-shapes have substantially the same angle when the
body member is unexpanded. In a further and/or alternative
non-limiting design, the angle formed by the V-shapes is between
0-90.degree. when the body member is unexpanded, typically about
10-75.degree., and more typically about 15-60.degree., and even
more typically about 15-45.degree.. In still a further and/or
alternative non-limiting design, a plurality of slots have a length
dimension that is at least about twice as great as the width
dimension of the slot when the body member is unexpanded, and
typically at least about 3 times as great, and more typically at
least about 5 times as great, and even more typically at least
about 10 times as great, and still even more typically at least
about 15 times as great. In yet a further and/or alternative
non-limiting design, a plurality of V-shapes in a set of V-shapes
are oriented in the same direction with respect to one another and
oriented such that the base of one V-shape is positioned from the
base of an adjacent V-shape a distance that is at least about 15%
of the length of the legs of the V-shaped slot, typically about
15-80% of the length of the slots forming a leg of the V-shape,
typically about 20-60% of the length of the leg of the V-shape, and
even more typically about 30-50% of the length of the leg of the
V-shape. In still yet a further and/or alternative non-limiting
design, a plurality of slots have a substantially oval shape. In
another and/or alternative non-limiting design, at least a
plurality of slots that form the V-shape do not intersect with one
another. In one particular design, none of the slots that form the
V-shape intersect with one another.
[0017] Still another and/or alternative feature of the present
invention is that the body member has a biocompatible coating that
is coated and/or impregnated on at least a portion of its wall
surface. The biocompatible coating can be used to reduce
inflammation, infection, irritation and/or rejection of the stent.
In one embodiment of the present invention, the biocompatible
coating includes, but is not limited to, a metal coating. In one
aspect of this embodiment, the metal coating is plated on at least
a portion of the stent. In another and/or alternative aspect of
this embodiment, the metal coating includes, but is not limited to,
gold, platinum, titanium, nickel, tin, or combinations thereof. In
another and/or alternative embodiment of the present invention, the
biocompatible coating includes, but is not limited to, a polymer
and/or a copolymer coating. In one aspect of this embodiment, the
polymer and/or a copolymer coating includes, but is not limited to,
polytetrafluoroethylene, polyethylene, poly(hydroxyethly
methacrylate), poly(vinyl alcohol), polycaprolactone, poly(D,
L-lactic acid), poly(L-lactic acid), poly(lactide-co-glycolide),
poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate),
polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid),
poly(glycolic acid-cotrimethylene cabonate), polyphosphoester,
polyphosphoester urethane, poly(amino acids), cyanoacrylates,
poly(trimethylene carbonate), poly(iminocarbonate),
copoly(ether-esters), polyalkylene oxalates, polyphosphazenes,
polyiminocarbonates, aliphatic polycarbonates, polyethylene oxide,
polyethylene gylcol, poly(propylene oxide), polyacrylamides,
polyacrylic acid (30-60% solution), polymethacrylic acid,
poly(N-vinyl-2-pyrollidone), polyurethanes, poly(aminoacid),
cellulosic polymers (e.g. sodium carboxymethyl cellulose,
hydroxyethyl celluslose), collagens, carrageenan, alginate, starch,
dextrin, gelatins, poly(lactide), poly(glycolide), polydioxanone,
polycaprolactone, polyhydroxybutyrate, poly(phospazazene),
poly(phosphate ester), poly(lactide-co-glycolide),
poly(glycolide-co-trimethylene carbonate),
poly(glycolide-co-caprolactone), polyanhydrides, polyamides,
polyesters, polyethers, polyketones, polyether elastomers,
parylene, polyether amide elastomers, polyacrylate-based
elastomers, polyethylene, polypropylene, and/or and derivatives
thereof. In one aspect of this embodiment, the polymer and/or
copolymer is substantially non-biodegradable so as to substantially
maintain its fluction throughout most or all of the useful life of
the stent. In another and/or alternative aspect of this embodiment,
one or more polymers are at least partially coated onto the surface
of the stent by a process disclosed in U.S. Pat. Nos. 5,355,832 and
5,447,799, which are incorporated herein by reference. In still
another and/or alternative embodiment of the present invention, the
biocompatible coating includes, but is not limited to, living
cells. In yet another and/or alternative embodiment of the
invention, the coating layer has a thickness in a range from about
50 to 500,000 Angstroms (.ANG.), and typically in the range from
about 100,000 to 500,000 .ANG..
[0018] Still yet another and/or alternative feature of the present
invention is that the stent, upon expansion, substantially
maintains its original longitudinal length. In one embodiment of
the present invention, the stent, upon expansion, substantially
maintains its original longitudinal length throughout the expansion
of the stent.
[0019] Another and/or alternative feature of the present invention
is that the stent includes at least two body members that are
connected together by at least one connector member that allows
transverse bending and flexibility invariant to the plane of
bending. In one embodiment of the present invention, the connector
member includes a non-linear portion. In one aspect of this
embodiment, the connector member is at least partially V-shaped
member (e.g., V-shaped, N-shaped, and/or M-shaped, W-shaped,
X-shaped, Y-shaped, Z-shaped, etc.) and/or U-shaped (e.g.,
U-shaped, S-shaped, etc.) member. In another and/or alternative
embodiment of the present invention, the two body members are
connected together by a plurality of connectors. In one aspect of
this embodiment, two or more of the connectors are spaced at
substantially equal distances from one another. In another and/or
alternative aspect of this embodiment, two or more of the
connectors are substantially symmetrically oriented from one
another. In still another and/or alternative aspect of this
embodiment, at least three connectors connect together two body
members, and typically about 3-20 connectors connect together two
body members, and even more typically about 3-10 connectors connect
together two body members. In still another and/or alternative
embodiment of the present invention, the size of the connector is
limited so as not to interfere with the proper expansion of the
stent. In one aspect of this embodiment, the substantially V-shaped
or U-shaped member has a height that is less than about five times
the maximum height of a polygonal shape in the unexpanded stent,
and typically less than about three times the maximum height of a
polygonal shape in the unexpanded stent, and more typically less
than about two times the maximum height of a polygonal shape in the
unexpanded stent, and even more typically less than about 1.75
times the maximum height of a polygonal shape in the unexpanded
stent, and yet even more typically less than about 1.5 times the
maximum height of a polygonal shape in the unexpanded stent, and
still yet even more typically less than about 1.3 times the maximum
height of a polygonal shape in the unexpanded stent. In another
and/or alternative aspect of this embodiment, the substantially
V-shaped or U-shaped member has a height that is less than about
1.5 times the maximum width of the V-shape in the unexpanded stent,
and typically less than about 1.0 times the maximum width of the
V-shape in the unexpanded stent, and more typically less than about
0.75 times the maximum width of the V-shape in the unexpanded
stent, and even more typically less than about 0.65 times the
maximum width of the V-shape in the unexpanded stent, and yet
typically less than about 0.5 times the maximum width of the
V-shape in the unexpanded stent, and still yet more typically less
than about 0.4 times the maximum width of the V-shape in the
unexpanded stent.
[0020] Yet another and/or alternative feature of the present
invention is that the body member is made of and/or includes a
material that is visible under fluoroscopy in vivo. The material to
increase visibility includes, but is not limited to, metals,
polymers and/or copolymers. In one embodiment of the present
invention, the material to increase visibility is adhered to the
surface of at least a portion of the stent by coating, plating,
mounting, welding and/or braising. In another and/or alternative
embodiment of the present invention, the material to increase
visibility is secured to the stent so as to principally come in
contact with the inner luminal surface of the body passageway. For
instance, when the stent is inserted into a blood vessel, the
material to increase visibility primarily contacts the inner
luminal surface of the blood vessel and not any blood-borne
components that could accelerate stent failure rates. In one aspect
of this embodiment, the material to increase visibility is at least
partially located on at least one end, and typically both ends, of
at least one body member. This positioning of the material on the
body member helps to identify the location of the ends of the body
member and the stent as a whole, thus enhancing the critical
placement of the stent so as to reduce the failure rate. In another
and/or alternative aspect of this embodiment, the material to
increase visibility is at least partially located on the outer
surface of the body member at one or more connector members of the
stent. This location of the material at one or more connector
members enhances the critical placement of the stent around areas
of high tortuosity so as to reduce the failure rate. In still
another and/or alternative embodiment of the present invention, the
material to increase visibility includes gold, gold alloy, and/or
tantalum, etc. In one aspect of this embodiment, the gold and/or
gold alloy is plated on at least a portion of the stent.
[0021] Still another and/or alternative feature of the present
invention is that the stent material is treated with gamma, beta
and/or e-beam radiation to reduce the vascular narrowing of the
stented section. The radiation treatment can inactivate the cell
migration and properties thereof within a 3 mm depth of the
arterial wall. The radiation treatment can further and/or
alternatively sterilize the stent to reduce infection when the
stent is inserted into a body passageway.
[0022] Another and/or alternative feature of the present invention
is that the stent can be inserted and expanded by standard
procedures. The stent is designed so it can be inserted into a body
passageway until it is disposed at the desired location within the
body passageway. The stent can then be radially expanded outwardly
into contact with the body passageway until the body passageway, at
the desired location, has been expanded, whereby the stent inhibits
or prevents the body passageway from collapsing. In one embodiment
of the present invention, the stent is at least partially expanded
by an angioplasty balloon.
[0023] Still another and/or alternative feature of the present
invention is a stent that includes rounded, smooth and/or blunt
surfaces that minimize and/or prevent damage to body passageways as
the stent is inserted into a body passageway and/or expanded in a
body passageway. The modified end surfaces are designed to reduce
the cutting and/or piercing of tissue as the stent is positioned in
and/or expanded in a body passageway. Typically, the path from the
point of entry into a body passageway, and the final position of
the stent in the body passageway, are not straight. As a result,
the stent is caused to be weaved through the body passageway to
reach the final position in the body passageway. This weaving of
the stent can result in the front ends, back ends, and/or side
walls of the stent to cut, scrape or otherwise damage tissue in the
body passageway as the stent is moved in the body passageway. The
rounding, smoothing and/or blunting of the surfaces significantly
reduces possible damage to the tissue. Damage to the tissue in the
body passageway can also occur during the expansion of the stent.
The rounding, smoothing and/or blunting of the surfaces likewise
significantly reduces possible damage to the tissue during the
expansion of the stent. In one embodiment of the present invention,
the rounding, smoothing and/or blunting of the surfaces can be
accomplished by a number of different procedures. Some of these
procedures include, but are not limited to, buffing, grinding,
and/or sanding the surfaces. In another and/or alternative
embodiment of the present invention, the surfaces of the stent are
smoothed by coating and/or impregnating the stent with one or more
metals or compounds. In one aspect of this embodiment, at least a
portion of the stent is coated and/or impregnated with a polymer
and/or copolymer so as to reduce or eliminate the sharp, rough,
and/or pointed surfaces on the stent.
[0024] A further and/or alternative feature of the present
invention is that the stent is at least partially coated and/or
impregnated with one or more vascular active agents that inhibit
and/or reduce restenosis, vascular narrowing and/or in-stent
restenosis. In one embodiment of the present invention, at least
one of the vascular active agents affects and/or alters tissue
contraction and/or expansion to inhibit and/or reduce restenosis,
vascular narrowing and/or in-stent restenosis. Prior substances
have been coated onto stents to address one or more problems
associated with the use of stents. These substances include
aspirin, heparin, colchicine and dexamethazone, among others. These
substances are used to inactivate platelets, stop cell division and
prevent cell adhesion. The problems associated with the use of
these substances have varied effects. Heparin is not potent enough
to extend a clinical effect. Colchicine has been shown to kill the
cells in the surrounding area and actually propagate the problem.
Dexamethazone has not provided the desired restenosis prevention.
As defined herein, the term "vascular active agent" is defined as a
substance other than aspirin, colchicine, dexamethazone, or
heparin. The vascular active agent is formulated to inhibit,
reduce, and/or prevent restenosis, vascular narrowing and/or
in-stent restenosis in a body passageway. As can be appreciated,
the vascular active agent can be used independent of or in
combination with a "secondary vascular active agent." In another
and/or alternative embodiment of the present invention, the
secondary vascular active agent includes, but is not limited to, an
agent that inhibits, reduces, and/or prevents thrombosis. Such
agent can include, but is not limited to, antithrombotic compounds,
anti-platelet compounds, and/or anti-coagulant compounds. In
addition, the "secondary vascular active agent" can include
compounds that include, but are not limited to, metabolic
inhibitors, antineoplastics, proliferation inhibitors, cytotoxic
compounds, antiplatelets, anti-coagulants, fribrinolytics, thrombin
inhibitors, antimitotics, anti-inflammatory compounds, radioactive
isotopes, and/or anti-tumor compounds. Furthermore, the "secondary
vascular active agent" can include, but is not limited to, DNA,
plasmid DNA, RNA, plasmid RNA, ACE inhibitors, growth factors,
cholesterol-lowering agents, vasodilating agents, oligonucleotides,
and/or anti-sense oligonucleotides. Specific secondary vascular
active agents that can be used include, but are not limited to,
aspirin, colchicine, heparin, glucocorticoids (e.g. dexamethazone,
betamethazone), hirudin, tocopherol, angiopeptin, D-Phe-ProArg
chloromethyl ketone, and/or derivatives of these compounds.
Heretofore, Applicant is unaware of stents being coated and/or
impregnated with a combination of at least one vascular active
agent and at least one secondary vascular active agent. In
addition, Applicant is unaware of stents being coated and/or
impregnated with a combination of two or more secondary vascular
active agents. Although the prior use of a single secondary
vascular active agent has not resolved problems associated with
in-stent restenosis, vascular narrowing and/or restenosis, the
combination of two or more of these compounds coated and/or
impregnated on the stent can provide better results. The scope of
this invention encompasses the concept of at least partially
coating and/or impregnating the stent with two or more secondary
vascular active agents by themselves or in combination with one or
more vascular active agents. In one aspect of this embodiment, the
vascular active agent includes a compound that at least partially
inhibits PDGF activity in the body passageway. After a stent is
inserted into a body passageway, the stent may induce some
irritation in the body passageway. The biological factor, PDGF, is
turned on due to such irritation and activates the components of
clotting. These components can cause clotting in the stent area or
in adjacent areas. This clotting can cause the body passageway to
narrow or ultimately close. At least one or more substances coated
and/or impregnated onto the stent are formulated to deactivate
and/or inhibit the activity of the PDGF, thereby reducing the
occurrence of in-stent restenosis, vascular narrowing and/or
restenosis. In another and/or alternative aspect of this
embodiment, at least one of the vascular active agents that is at
least partially coated and/or impregnated onto the stent to inhibit
PDGF activity in the body passageway includes triazolopyrimidime
(Trapidil), prostacyclin, and/or derivatives thereof. When the
stent is inserted into a body passageway, some damage to the tissue
of the body passageway can occur. For instance, a damaged
endothelium exposes the connective tissue to platelet aggregation
and to local release of PDGF. Numerous animal models have shown
that platelet adhesion to the vascular wall of this damaged
endothelium soon triggers the proliferation and migration of smooth
muscle cells. If platelets are a source of PDGF, it has now been
demonstrated that endothelial cells, macrophages and smooth muscle
cells are also a source of PDGF following vascular trauma. The
influence of Trapidil on platelet aggregation is linked to
inhibition of the synthesis of thromboxane A2 and the partial
blocking of thromboxane A2 receptors. Trapidil is able to normalize
an incorrect balance between thromboxane A2 and prostacycline.
Thromboxane A2 is a powerful inducer of platelet aggregation.
Thromboxane A2 is also responsible for the contraction of smooth
muscles or vessels and stimulates the proliferation of the arterial
intimal cells. Prostacyclin also inhibits platelet aggregation and
has vasodilator properties. Trapidil also has antithrombotic
properties and can significantly reduce thrombosis induced by
creation of an arteriovenous conduit, as compared to aspirin and
dipyridamoles, which only had a modest effect. Trapidil has other
desirable properties such as vasodilation, a decrease in angina and
an increase in HDL levels in patients with ischemic heart disease.
Trapidil also effectively inhibits restenosis. Trapidil has an
affinity to exert clinical effects starting in the second hour of
treatment. The platelet inhibition in the first day of treatment
with Trapidil continues through the thirtieth day. The philosophy
of a multifactorial approach, including but not limited to the
increasing success of angioplasty and stent associated with a
considerable reduction in complications, promotes the use of this
technique in a large scale in the treatment of patients with
coronary heart disease. Restenosis is one of the most important
limitations to the long term benefits of angioplasty and a stent
combination. A pharmacological approach aiming to intervene in the
mechanism of restenosis is needed to supplement the mechanical
approach of the revascularization procedure. Various approaches
have been proposed for the prevention of restenosis. The use of
drugs such as, but not limited to, Trapidil, delivered by a stent
locally to the affected area satisfies this need. As can be
appreciated, Trapidil can be used in combination with one or more
other vascular active agents and/or in combination with one or more
secondary vascular active agents. The amount of Trapidil coated
and/or impregnated into the stent can be varied depending on the
intended use of the stent and/or size of the stent. In still
another and/or alternative embodiment of the present invention, the
stent includes up to about 200 mg of Trapidil. In one aspect of
this embodiment, the stent includes at least about 1 .mu.g of
Trapidil. In another and/or alternative aspect of this embodiment,
the stent includes about 10 .mu.g to about 50 mg of Trapidil. In
still another and/or alternative aspect of this embodiment, the
stent includes about 20 .mu.g to about 10 mg of Trapidil.
[0025] Still a further and/or alternative feature of the present
invention is that the stent is at least partially coated and/or
impregnated with one or more vascular active agents that promote
blood vessel growth. The fully or partially blocked blood vessel
and tissue about the fully or partially blocked blood vessel become
oxygen starved due to the impaired flow of blood through the fully
or partially blocked blood vessels. When a stent in inserted into
the blood vessel to reestablish a more normal blood flow rate
through the blood vessel, the region around the formerly fully or
partially blocked blood vessel once again begins to receive a
proper oxygen supply. However, prolonged oxygen starvation can
damage the blood vessels and surrounding tissue to an extent that a
substantial time period is required to naturally repair such
damaged tissue. Furthermore, the formerly blocked or partially
blocked blood vessel may be weaker resulting in further damage to
the blood vessel once normal blood flow rates are reestablished.
Many of these problems can be addressed by at least partially
coating and/or impregnating the stent with one or more vascular
active agents that promote blood vessel growth. One non-limiting
blood vessel growth promoter that can be coated and/or, impregnated
on the stent is granulo-cyte-macrophage colony-stimulating-factor
(GM-CSF). GM-CSF has been found to simulate blood vessel growth
even in oxygen starved environments. As can be appreciated, GM-CSF
can be used in combination with one or more other vascular active
agents and/or in combination with one or more secondary vascular
active agents. The amount of GM-CSF coated and/or impregnated into
the stent can be varied depending on the intended use of the stent
and/or size of the stent. In one embodiment of the present
invention, the stent includes up to about 200 mg of GM-CSF. In one
aspect of this embodiment, the stent includes at least about 1
.mu.g of GM-CSF. In another and/or alternative aspect of this
embodiment, the stent includes about 10 .mu.g to about 50 mg of
GM-CSF. In still another and/or alternative aspect of this
embodiment, the stent includes about 20 .mu.g to about 10 mg of
GM-CSF.
[0026] Yet another and/or alternative feature of this invention
corresponds to the local delivery of one or more vascular active
agents to inhibit and/or prevent restenosis, vascular narrowing
and/or in-stent restenosis including, but not limited to, Trapidil,
and/or GM-CSF, through an angioplasty balloon with the physical
capability to transfer solute of the vascular active agent through
the angioplasty balloon membrane to the affected sight. As can be
appreciated, a vascular active agent such as, but not limited to,
Trapidil and/or GM-CSF, can be delivered alone and/or in
combination with another vascular active agent and/or a secondary
vascular active agent. This delivery can be in the form of a
stream, a slow oozing delivery or a bolus injection. The delivery
can be made through magnetic, electrical or physical arrangements.
In one embodiment of the present invention, the delivery of a
vascular active agent and/or secondary vascular active agent is
accomplished through a separate passageway capable of channeling
the solute of the vascular active agent and/or secondary vascular
agent to the affected area. This delivery through an angioplasty
balloon also delivers the vascular active agent and/or secondary
vascular active agent to the sight of restenosis, vascular
narrowing, in-stent restenosis, thrombosis and the like, and/or to
the site to promote growth of blood vessels. In one aspect of this
embodiment, the angioplasty balloon includes one or more slits or
openings wherein the vascular active agent and/or secondary
vascular active agent can stream, ooze or otherwise flow out of the
angioplasty balloon and into the body passageway. The one or more
slits and/or openings can be designed so as to allow the vascular
active agent and/or secondary vascular active agent to exit the
angioplasty balloon when the angioplasty balloon is in an expanded
and unexpanded state. In one non-limiting design, the one or more
slits and/or openings in the angioplasty balloon inhibit or prevent
the vascular active agent and/or secondary vascular active agent
from entering the body passageway when the angioplasty balloon is
in the unexpanded state.
[0027] Another and/or alternative feature of the present invention
is that one or more vascular active agents and/or secondary
vascular active agents are at least partially coated and/or
impregnated totally on or partially on the stent. In one embodiment
of the present invention, the thickness of the coating on the stent
can be uniform or varied. Generally, the thickness of the coating
is not as important as the concentration of the vascular active
agent and/or secondary vascular active agent needed to acquire the
desired affect. High concentrations of vascular active agents
and/or secondary vascular active agents can be coated with thinner
coatings, and lower concentrations of vascular active agents and/or
secondary vascular active agents can be coated with thicker
coatings. In one aspect of this embodiment, the coating thickness
is less than or equal to the material that forms the stent. In
another and/or alternative embodiment of the invention, the stent
includes a single coating on specific regions of the stent or on
the total surface of the stent. In one aspect of this embodiment,
the composition of the coating on different regions of the stent is
substantially the same. In another and/or alternative aspect of
this embodiment, the composition of the coating on different
regions of the stent is different. In still another and/or
alternative embodiment of the present invention, the stent includes
a multiple coatings on specific regions of the stent or on the
total surface of the stent. In one aspect of this embodiment, the
coating thicknesses are of the multiple coatings are substantially
the same. In another and/or alternative aspect of this embodiment,
the coating thickness of the two or more coatings is different. In
still another and/or alternative aspect of this embodiment, the
composition of the coatings is substantially the same. In yet
another and/or alternative aspect of this embodiment, the
composition of two or more coatings is different. In yet another
and/or alternative embodiment of the present invention, one or more
coatings are applied to the stent by vaporization, plasma
deposition, ionization, dipping, brushing, and/or spraying. In
still yet another and/or alternative embodiment of the invention,
the vascular active agent and/or secondary vascular active agent is
at least partially impregnated into the stent. The impregnation can
be the result of a porous surface of the stent and/or the stent
including one or more internal cavities. In one aspect of this
embodiment, the stent is impregnated on specific regions of the
stent or on the total surface of the stent. In another and/or
alternative aspect of this embodiment, the stent is impregnated
with the same compound. In still another and/or alternative aspect
of this embodiment, the stent is impregnated with different
compounds at different regions of the stent. In yet another and/or
alternative aspect of this embodiment, the stent is impregnated
with multiple compounds. In a further and/or alternative embodiment
of the present invention, one or more compounds are impregnated in
the stent by vaporization, ionization, dipping, brushing, and/or
spraying.
[0028] Still another and/or alternative feature of the present
invention is that one or more vascular active agents and/or
secondary vascular active agents are at least partially coated
and/or impregnated onto the stent by the use of an intermediate
compound. Typically, the intermediate compound is a synthetic
biocompatible material that does not adversely affect the vascular
active agent and/or secondary vascular active agent or cause
problems or adverse reactions in the body passageway. In one
embodiment of the present invention, the intermediate compound is
biodegradable. In another and/or alternative embodiment of the
present invention, the intermediate compound is non-biodegradable.
In still another and/or alternative embodiment of the invention,
the intermediate compound is at least partially coated and/or
impregnated on specific regions of the stent or totally coats the
stent. In one aspect of this embodiment, the thickness of the
coating on the stent can be uniform or varied. The coating
thickness can be used to control the amount of vascular active
agent and/or secondary vascular active agent that is coated on the
stent and/or to control the release rate of the vascular active
agent from the stent. Thicker coating can hold more vascular active
agent and/or secondary vascular active agent. Thicker coating can
also increase the time of full release of the vascular active agent
and/or secondary vascular active agent from the stent. In one
particular non-limiting design, the coating thickness is less than
or equal to the material that forms the stent. In another and/or
alternative embodiment of the invention, the stent includes a
single coating of intermediate compound on specific regions of the
stent or on the total surface of the stent. In one aspect of this
embodiment, the composition of the intermediate compound on
different regions of the stent is substantially the same. In
another and/or alternative aspect of this embodiment, the
composition of the intermediate compound on different regions of
the stent is different. In still another and/or alternative
embodiment of the present invention, the stent includes a multiple
coatings of intermediate compound on specific regions of the stent
or on the total surface of the stent. In one aspect of this
embodiment, the coating thicknesses of the intermediate compound
are substantially the same. In another and/or alternative aspect of
this embodiment, the coating thickness of two or more coatings of
intermediate compound is different. In still another and/or
alternative aspect of this embodiment, the composition of the
coatings of intermediate compound is substantially the same. In yet
another and/or alternative aspect of this embodiment, the
composition of two or more coatings of intermediate compound are
different. In yet another and/or alternative embodiment of the
present invention, one or more coatings of intermediate compound
are applied to the stent by vaporization, ionization, dipping,
brushing, and/or spraying. In yet another and/or alternative
embodiment of the invention, the intermediate compound is at least
partially impregnated into the stent. The impregnation can be the
result of a porous surface of the stent and/or the stent including
one or more internal cavities. In one aspect of this embodiment,
the stent is impregnated with the intermediate compound on specific
regions of the stent or on the total surface of the stent. In
another and/or alternative aspect of this embodiment, the stent is
impregnated with the same intermediate compound. In still another
and/or alternative aspect of this embodiment, the stent is
impregnated with different intermediate compounds at different
regions of the stent. In yet another and/or alternative aspect of
this embodiment, the stent is impregnated with multiple
intermediate compounds. In a further and/or alternative embodiment
of the present invention, one or more intermediate compounds are
impregnated in the stent by vaporization, ionization, dipping,
brushing, and/or spraying. In still a further and/or alternative
embodiment of the present invention, the one or more vascular
active agents and/or secondary vascular active agents are coated
and/or impregnated onto the stent prior to coating and/or
impregnating the stent with one or more intermediate compounds. In
yet a further and/or alternative embodiment of the present
invention, the one or more intermediate compounds are coated and/or
impregnated onto the stent prior to coating and/or impregnating the
stent with one or more vascular active agents and/or secondary
vascular active agents.
[0029] Still yet another and/or alternative feature of the present
invention is that the stent is at least partially coated and/or
impregnated with, and/or at least partially includes one or more
biological agents. The biological agent can be directly coated
and/or impregnated on to the stent, and/or coated with the
assistance of one or more intermediate compounds. In one embodiment
of the present invention, the thickness of the coating of the
biological agent on the stent can be uniform or varied. Generally,
the thickness of the coating is not as important as the
concentration of the vascular active agent and/or secondary
vascular active agent needed to acquire the desired affect. High
concentrations of biological agent can be coated with thinner
coatings, and lower concentrations of biological agent can be
coated with thicker coatings. In one aspect of this embodiment, the
coating thickness is less than or equal to the material that forms
the stent. In another and/or alternative embodiment of the
invention, the stent includes a single coating on specific regions
of the stent or on the total surface of the stent. In one aspect of
this embodiment, the composition of the coating on different
regions of the stent is substantially the same. In another and/or
alternative aspect of this embodiment, the composition of the
coating on different regions of the stent is different. In still
another and/or alternative embodiment of the present invention, the
stent includes multiple coatings on specific regions of the stent
or on the total surface of the stent. In one aspect of this
embodiment, the coating thicknesses of the multiple coatings are
substantially the same. In another and/or alternative aspect of
this embodiment, the coating thickness of the two or more coatings
is different. In still another and/or alternative aspect of this
embodiment, the composition of the coatings is substantially the
same. In yet another and/or alternative aspect of this embodiment,
the composition of two or more coatings is different. In yet
another and/or alternative embodiment of the present invention, one
or more coatings of biological agent are applied to the stent by
vaporization, ionization, dipping, brushing, and/or spraying. In
still yet another and/or alternative embodiment of the invention,
the biological agent is at least partially impregnated into the
stent. The impregnation can be the result of a porous surface of
the stent and/or the stent including one or more internal cavities.
In one aspect of this embodiment, the stent is impregnated on
specific regions of the stent or on the total surface of the stent.
In another and/or alternative aspect of this embodiment, the stent
is impregnated with the same compound. In still another and/or
alternative aspect of this embodiment, the stent is impregnated
with different compounds at different regions of the stent. In yet
another and/or alternative aspect of this embodiment, the stent is
impregnated with multiple compounds. In a further and/or
alternative embodiment of the present invention, one or more
compounds are impregnated in the stent by vaporization, ionization,
dipping, brushing, and/or spraying. As defined herein, the term
"biological agent" is defined as any substance, drug or otherwise,
that is formulated or designed to prevent, inhibit and/or treat one
or more biological problems, such as, but not limited to, viral,
fungus and/or bacteria infection; vascular disorders; digestive
disorders; reproductive disorders; lymphatic disorders; cancer;
implant rejection; pain; nausea; swelling; arthritis; bone disease;
organ failure; immunity diseases; cholesterol problems; blood
diseases; lung diseases and/or disorders; heart diseases and/or
disorders; brain diseases and/or disorders; neuroglial diseases
and/or disorders; kidney diseases and/or disorders; ulcers; liver
diseases and/or disorders; intestinal diseases and/or disorders;
gallbladder diseases and/or disorders; pancreatic diseases and/or
disorders; psychological disorders; respiratory disorders; gland
disorders; skin diseases; hearing disorders; oral disorders; nasal
disorders; eye disorders; fatigue; genetic disorders; bums; scars;
trauma; weight disorders; addiction disorders; hair loss; cramps;
muscle spasms; tissue repair; and/or the like. As such, the term
"biological agent" includes vascular active agents and secondary
vascular active agents.
[0030] Still another and/or alternative feature of the present
invention is that the biological agent is at least partially coated
and/or impregnated onto the stent by the use of an intermediate
compound. Typically, the intermediate compound is a synthetic
biocompatible material that does not adversely affect the
biological agent or cause problems or adverse reactions in the body
passageway. In one embodiment of the present invention, the
intermediate compound is biodegradable. In another and/or
alternative embodiment of the present invention, the intermediate
compound is non-biodegradable. In still another and/or alternative
embodiment of the invention, the intermediate compound is at least
partially coated and/or impregnated on specific regions of the
stent or totally coats the stent. In one aspect of this embodiment,
the thickness of the coating on the stent can be uniform or varied.
The coating thickness can be used to control the amount of
biological agent that is coated on the stent and/or to control the
release rate of the biological agent from the stent. Thicker
coating can hold more biological agent. Thicker coating can also
increase the time of full release of the biological agent from the
stent. In one particular non-limiting design, the coating thickness
is less than or equal to the material that forms the stent. In
another and/or alternative embodiment of the invention, the stent
includes a single coating of intermediate compound on specific
regions of the stent or on the total surface of the stent. In one
aspect of this embodiment, the composition of the intermediate
compound on different regions of the stent is substantially the
same. In another and/or alternative aspect of this embodiment, the
composition of the intermediate compound on different regions of
the stent is different. In still another and/or alternative
embodiment of the present invention, the stent includes a multiple
coatings of intermediate compound on specific regions of the stent
or on the total surface of the stent. In one aspect of this
embodiment, the coating thicknesses of the intermediate compound
are substantially the same. In another and/or alternative aspect of
this embodiment, the coating thickness of two or more coatings of
intermediate compound is different. In still another and/or
alternative aspect of this embodiment, the composition of the
coatings of intermediate compound is substantially the same. In yet
another and/or alternative aspect of this embodiment, the
composition of two or more coatings of intermediate compound are
different. In yet another and/or alternative embodiment of the
present invention, one or more coatings of intermediate compound
are applied to the stent by vaporization, ionization, dipping,
brushing, and/or spraying. In yet another and/or alternative
embodiment of the invention, the intermediate compound is at least
partially impregnated into the stent. The impregnation can be the
result of a porous surface of the stent and/or the stent including
one or more internal cavities. In one aspect of this embodiment,
the stent is impregnated with the intermediate compound on specific
regions of the stent or on the total surface of the stent. In
another and/or alternative aspect of this embodiment, the stent is
impregnated with the same intermediate compound. In still another
and/or alternative aspect of this embodiment, the stent is
impregnated with different intermediate compounds at different
regions of the stent. In yet another and/or alternative aspect of
this embodiment, the stent is impregnated with multiple
intermediate compounds. In a further and/or alternative embodiment
of the present invention, one or more intermediate compounds are
impregnated in the stent by vaporization, ionization, dipping,
brushing, and/or spraying. In still a further and/or alternative
embodiment of the present invention, the one or more biological
agents are coated and/or impregnated onto the stent prior to
coating and/or impregnating the stent with one or more intermediate
compounds. In yet a further and/or alternative embodiment of the
present invention, the one or more intermediate compounds are
coated and/or impregnated onto the stent prior to coating and/or
impregnating the stent with one or more biological agents.
[0031] A further another and/or alternative feature of the present
invention is that the biological agent is at least partially
encapsulated by a material. In one embodiment of the present
invention, the biological agent includes one or more vascular
active agents and/or one or more secondary vascular active agents
to inhibit and/or reduce restenosis, vascular narrowing and/or
in-stent restenosis. In another and/or alternative embodiment of
the present invention, the biological agent is at least partially
encapsulated in biodegradable polymer and/or copolymer. In one
aspect of this embodiment, the polymer and/or copolymer is at least
partially formulated from aliphatic polyester compounds such as,
but not limited to, PLA (i.e. poly(D, L-lactic acid), poly(L-lactic
acid)) and/or PLGA (i.e. poly(lactide-co-glycoside)). In still
another and/or alternative embodiment of the present invention, the
rate of degradation of the polymer and/or copolymer is principally
a function of 1) the water permeability and solubility of the
polymer and/or copolymer, 2) chemical composition of the polymer
and/or copolymer, 3) mechanism of hydrolysis of the polymer and/or
copolymer, 4) the biological agent encapsulated in the polymer
and/or copolymer, 5) the size, shape and surface volume of the
polymer and/or copolymer, 6) porosity of the polymer and/or
copolymer, and/or 7) the molecular weight of the polymer and/or
copolymer. As can be appreciated, other factors may also affect the
rate of degradation of the polymer and/or copolymer. The rate of
degradation of the polymer and/or copolymer controls the amount of
biological agent released during a specific time period into the
body passageway or other parts of the body. As can be appreciated,
the biological agent can be formed into a pill, capsule or the like
for oral ingestion by a human or animal. The rate of degradation of
the polymer and/or copolymer that is at least partially
encapsulating the biological agent controls the amount of
biological agent that is released into a body passageway or other
part of the body over time. The biological agent can be at least
partially encapsulated with different polymer and/or copolymer
coating thickness, different numbers of coating layers, and/or with
different polymers or copolymers to alter the time period one at
least partially encapsulated biological agent is released in a body
passageway or other part of the body over time as compared to
another at least partially encapsulated biological agent.
Alternatively or in addition, one or more at least partially
encapsulated biological agents can be at least partially
encapsulated in a biodegradable capsule and/or coating, which
biodegradable capsule and/or coating delays the exposure of one or
more of the at least partially encapsulated biological agents to
fluids in a body passageway or other part of the body. As can
further be appreciated, the at least partially encapsulated
biological agent can be introduced into a human or animal by means
other than by oral introduction, such as, but not limited to,
injection, topical applications, intravenously, eye drops, nasal
spray, surgical insertion, suppositories, intrarticularly,
intraocularly, intranasally, intradermally, sublingually,
intravesically, intrathecally, intraperitoneally, intracranially,
intramuscularly, subcutaneously, directly at a particular site, and
the like. In another aspect of this embodiment, the polymer and/or
copolymer is formed into one or more shapes such as, but not
limited to, spherical, cubical, cylindrical, pyramidal, and the
like.
[0032] Yet a further another and/or alternative feature of the
present invention is that the stent is at least partially coated
and/or impregnated with one or more polymers or copolymers that
include one or more biological agents. In one embodiment of the
present invention, the coating thickness of each intermediate
compound on the stent is less than about 0.08 inch, and typically
less than about 0.01 inch, and even more typically less than about
0.005 inch. The particular coating sequence on a stent will
generally depend on 1) the amount of a particular biological agent
to be released over time, 2) the sequence of biological agents to
be released over time, 3) the time period the release of the
biological agent is to begin, 4) the time period the release of the
biological agent is to end, and/or 5) the location in the body the
biological agent is to be released. As can be appreciated, other
factors may dictate the particular coating sequence on a stent. In
another and/or alternative embodiment of the present invention, the
intermediate compound is formulated to delay and/or regulate the
time and/or amount of one or more biological agents being released
into the body passageway, and/or to facilitate in the bonding of
one or more biological agents to the stent. The intermediate
compound can be formulated so as to form one or more bonds with one
or more biological agents or be chemically inert with respect to
one or more biological agents.
[0033] Still a further another and/or alternative feature of the
present invention is that the stent is at least partially formed by
a material that includes one or more biological agents. In one
embodiment of the present invention, one or more biological agents
are at least partially embedded in the stent so as to inhibit the
release, control the release, and/or delay the release of one or
more biological agents into the body passageway. The material
forming at least a portion of the stent in which one or more
biological agents are imbedded can be a biodegradable material
and/or a non-biodegradable material. The material can be formulated
so as to form one or more bonds with one or more biological agents
or be chemically inert with respect to one or more biological
agents. Typically, the material is a substantially
non-biodegradable material so that the structural integrity of the
stent or other implant is maintained throughout the life of the
stent or other implant. However, there may be instances wherein the
stent or other implant advantageously becomes fully or partially
degraded over time. In one aspect of this embodiment, the material
includes a metal and/or polymer and/or copolymer.
[0034] Still a further another and/or alternative feature of the
present invention is that one or more biological agents at least
partially forms a chemical bond with an intermediate compound that
at least partially encapsulates one or more of the biological
agents; that at least partially coats and/or impregnates the stent
or other implant; and/or that at least partially forms the stent or
other implant. In one embodiment of the present invention, one or
more of the biological agents forms a polymer and/or copolymer salt
complex with one or more intermediate compounds that at least
partially encapsulates one or more of the biological agents; that
at least partially coats and/or impregnates the stent or other
implant; and/or that at least partially forms the stent or other
implant. In one aspect of this embodiment, the biological agent
includes, but is not limited to, Trapidil and/or derivatives
thereof; GM-CSF and/or derivatives thereof; taxol and/or
derivatives thereof (e.g. taxotere, baccatin, 10-deacetyltaxol,
7-xylosyl-10-deacetyltaxol, cephalomannine, 10-deacetyl-7-epitaxol,
7 epitaxol, 10-deacetylbaccatin III, 10-deacetylcephaolmannine);
5-Fluorouracil and/or derivatives thereof; Beta-Estradiol and/or
derivatives thereof; Tranilast and/or derivatives thereof; Probucol
and/or derivatives thereof; Angiopeptin and/or derivatives thereof;
paclitaxel and/or derivatives thereof; cytochalasin and/or
derivatives thereof (e.g. cytochalasin A, cytochalasin B,
cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F,
cytochalasin G, cytochalasin H, cytochalasin J, cytochalasin K,
cytochalasin L, cytochalasin M, cytochalasin N, cytochalasin O,
cytochalasin P, cytochalasin Q, cytochalasin R, cytochalasin S,
chaetoglobosin A, chaetoglobosin B, chaetoglobosin C,
chaetoglobosin D, chaetoglobosin E, chaetoglobosin F,
chaetoglobosin G, chaetoglobosin J, chaetoglobosin K, deoxaphomin,
proxiphomin, protophomin, zygosporin D, zygosporin E, zygosporin F,
zygosporin G, aspochalasin B, aspochalasin C, aspochalasin D);
aspirin and/or derivatives thereof; dipyridamoles and/or
derivatives thereof; argatroban and/or derivatives thereof;
forskolin and/or derivatives thereof; vapiprost and/or derivatives
thereof; prostacyclin and prostacyclin and/or derivatives thereof;
glycoprotein Ilb/Illa platelet membrane receptor antibody;
colchicine and/or derivatives thereof; dexamethazone and/or
derivatives thereof; dipyridamoles and/or derivatives thereof;
and/or heparin and/or derivatives thereof; glucocorticoids (e.g.
dexamethasone, betamethasone)and/or derivatives thereof; hirudin
and/or derivatives thereof; coumadin and/or derivatives thereof;
prostacyclenes and/or derivatives thereof; antithrombogenic agents;
steroids; seramin and/or derivatives thereof; thioprotese
inhibitors; nitric oxide; ibuprofen; antimicrobials; antibiotics;
tissue plasma activators; rifamycin and/or derivatives thereof;
monoclonal antibodies; antifibrosis compounds; cyclosporine;
hyaluronate; protamine and/or derivatives thereof; tocopherol
and/or derivatives thereof; angiopeptin and/or derivatives thereof;
tick anticoagulant protein and/or derivatives thereof; methotrexate
and/or derivatives thereof; azathioprine and/or derivatives
thereof; vincristine and/or derivatives thereof; vinblastine and/or
derivatives thereof; fluorouracil and/or derivatives thereof;
adriamycin and/or derivatives thereof; mutamycin and/or derivatives
thereof; Anti-Invasive Factor; Cartilage-Derived Inhibitor;
retinoic acids and/or derivatives thereof, Suramin; Tissue
Inhibitor of Metalloproteinase-1 and/or derivatives thereof; Tissue
Inhibitor of Metalloproteinase-2 and/or derivatives thereof;
Plasminogen Activator Inhibitor-1 and/or derivatives thereof;
Plasminogen Activator Inhibitor-2 and/or derivatives thereof;
estramustine and/or derivatives thereof; methotrexate and/or
derivatives thereof, curacin-A and/or derivatives thereof;
epothilone and/or derivatives thereof; vinblastine and/or
derivatives thereof; tBCEV and/or derivatives thereof; lighter "d
group" transition metals (e.g ammonium metavanadate, sodium
metavanadate, sodium orthovanadate, vanadyl acetylacetonate,
vanadyl sulfate mono- and trihydrates, ammonium tungstate, calcium
tungstate, sodium tungstate dihydrate, tungstic acid, tungsten (IV)
oxide, tungsten (VI) oxide, ammonium molybdate and its hydrates,
sodium molybdate and its hydrates, potassium molybdate and its
hydrates, molybdenum (VI) oxide, molybdenum (VI) oxide, molybdic
acid, molybdenyl acetylacetonate); Platelet Factor 4; growth
factors (e.g. VEGF; TGF; IGF; PDGF; FGF); Protamine Sulphate
(Clupeine); Sulphated Chitin Derivatives; Sulphated Polysaccharide
Peptidoglycan Complex; Staurosporine; proline analogs
(L-azetidine-2-carboxylic acid (LACA); cishydroxyproine;
d,L-3,4-dehydroproline; Thiaproline; alpha-dipyridyl; beta
aminopropionitrile fumarate;
4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone; Methotrexate
Mitoxantrone; Interferons; alpha 2 Macroglobulin; ChIMP-3;
Chymostatin; beta-Cyclodextrin Tetradecasulfate; Eponemycin;
Camptothecin; Fumagillin; Gold Sodium Thiomalate; D-Penicillamine;
beta-1-anticollagenase; alpha 2-antiplasmin; Bisantrene; Lobenzarit
disodium (N-(2)-carboxyphenyl-4-chloroanthronilic acid disodium;
Thalidomide; Angiostatic steroid; AGM-1470; carboxynaminolmidazole;
penicillins; cephalosporins (e.g. cefadroxil, cefazolin, cefaclor);
aminoglycosides (e.g. gentamycin, tobramycin; sulfonamides (e.g.
sulfamethoxazole); rapamycin, metronidazole; prednisone;
prednisolone;hydrocortisone; adrenocorticotropic hormone;
sulfasalazine; naproxen; fenoprofen; indomethacin; phenylbutazone;
acyclovir; ganciclovir; zidovudine; nystatin; ketoconazole;
griseofulvin; flucytosine; miconazole; clotrimazole; pentamidine
isethionate; quinine; chloroquine; mefloquine; thyroid hormone;
estrogen; progesterone; cortisone; growth hormone; insulin; T.sub.H
1 (e.g., Interleukins-2, -12, and -15, gamma interferon); T.sub.H 2
(e.g. Interleukins-4 and -10) cytokines); estramustine; epothilone;
curacin-A; colchicine; methotrexate; vinblastine;
4-tert-butyl->3-(2-chloroethyl)ureido!benze- ne ("tBCEU");
alpha-adrenergic blocking agents; angiotensin II receptor
antagonists; receptor antagonists for histamine; serotonin;
serotonin blockers; endothelin; inhibitors of the sodium/hydrogen
antiporter (e.g., amiloride and derivatives thereof); agents that
modulate intracellular Ca.sup.2+ transport such as L-type (e.g.,
diltiazem, nifedipine, verapamil) or T-type Ca.sup.2+ channel
blockers (e.g. amiloride); calmodulin antagonists (e.g., H.sub.7);
inhibitors of the sodium/calcium antiporter (e.g. amiloride); ap-1
inhibitors (for tyrosine kinases, protein kinase C, myosin light
chain kinase, Ca.sup.2+/calmodulin kinase II, casein kinase II);
anti-depressants (e.g. amytriptyline, fluoxetine, LUVOX.RTM. and
PAXIL.RTM.); cytokine and/or growth factors as well as their
respective receptors, (e.g., the interleukins, alpha, beta or
gamma-IFN (interferons), GM-CSF, G-CSF, epidermal growth factor,
transforming growth factors alpha and beta, TNF, and antagonists of
vascular epithelial growth factor, endothelial growth factor,
acidic or basic fibroblast growth factors, and platelet derived
growth factor); inhibitors of the IP.sub.3 receptor; protease;
collagenase inhibitors; nitrovasodilators (e.g. isosorbide
dinitrate); anti-mitotic agents (e.g. colchicine, anthracyclines
and other antibiotics, folate antagonists and other
anti-metabolites, vinca alkaloids, nitrosoureas, DNA alkylating
agents, topoisomerase inhibitots, purine antagonists and analogs,
pyrimidine antagonists and analogs, alkyl sulfonates);
immunosuppressive agents (e.g. adrenocorticosteroids,
cyclosporine); sense or antisense oligonucleotides (e.g. DNA, RNA,
plasmid DNA, plasmid RNA, nucleic acid analogues (e.g. peptide
nucleic acids); inhibitors of transcription factor activity (e.g.
lighter d group transition metals); anti-neoplastic compounds;
chemotherapeutic compounds (e.g. 5-fluorouracil, vincristine,
vinblastine, cisplatin, doxyrubicin, adriamycin, or tamocifen),
radioactive agents (e.g. Cu-64, Ca-67, Cs-131, Ga-68, Zr-89, Ku-97,
Tc-99m, Rh-105, Pd-103, Pd-109, In-111, I-123, I-125, I-131,
Re-186, Re-188, Au-198, Au-199, Pb-203, At-211, Pb-212, Bi-212,
H.sub.3P.sup.32O.sub.4); 7E-3B; CAPTOPRIL; CILAZAPRIL; LISINOPRIL;
LOVASTATIN; nitroprusside; phosphodiesterase inhibitors;
prostaglandin inhibitors; thioprotesase inhibitors;
triazolopyrimidine and/or derivatives thereof; calcium channel
blockers; toxins (e.g. ricin, abrin, diphtheria toxin, cholera
toxin, gelonin, pokeweed antiviral protein, tritin, Shigella toxin,
and Pseudomonas exotoxin A); metalloproteinase inhibitors; ACE
inhibitors; growth factors; oligonucleotides; antiplatlet
compounds; antitabolite compounds; anti-inflammatory compounds;
anticoagulent compounds; antimitotic compounds; antioxidants;
antimetabolite compounds (e.g staurosporin, trichothecenes, and
modified diphtheria and ricin toxins, Pseudomonas exotoxin);
anti-migratory agents (e.g. caffeic acid derivatives, nilvadipine);
anti-matrix compounds (e.g. colchicine, tamoxifen); protein kinase
inhibitors (e.g staurosporin); anti-vital compounds,
anti-proliferatives, anti-fungal compounds and/or anti-protozoal
compounds. As can be appreciated, the biological agent can include
other compounds. In one aspect of this embodiment, the Trapidil
forms a salt complex with the intermediate compound such that the
Trapidil forms the cationic component and the coating compound
forms the anionic component.
[0035] Still another and/or alternative feature of the present
invention, the intermediate compound used to at least partially
encapsulate one or more biological agents; at least partially coat
and/or impregnate the stent or other implant; and/or at least
partially form the stent or other implant is a polymer and/or
copolymer. In one embodiment of the present invention, the polymer
and/or copolymer includes one or more carboxylate groups, phosphate
groups, sulfate groups, and/or other organic anion groups. In one
aspect of this embodiment, the polymer and/or copolymer includes
one or more groups which form one or more anionic bonding sites for
cationic salts of the biological agent. In one aspect of this
embodiment, the polymer and/or copolymer includes one or more
groups that form one or more cationic bonding sites for anionic
salts of the biological agent. In one specific example of this
aspect, the polymer and/or copolymer includes one or more amine
groups and the like. In still another and/or alternative embodiment
of the present invention, the polymer and/or copolymer includes one
or more hydrophobic and/or hydrophilic groups. As can be
appreciated, the polymer and/or copolymer can include only
hydrophobic groups, only hydrophilic groups, or include a
combination hydrophobic groups and hydrophilic groups. Furthermore,
it can be appreciated that the hydrophobic and/or hydrophilic
groups in the polymer and/or copolymer can be the same or
different. Non-limiting examples of hydrophilic groups include
carboxylate groups (e.g. acrylate groups, methacrylate groups),
alcohol groups, sulfate groups, and the like. Specific non-limiting
examples include acrylic acid groups, methacrylic acid groups,
and/or maleic acid groups. Non-limiting examples of hydrophobic
groups include ethylene groups, vinyl groups, styrene groups,
propylene groups, urethane groups, ester groups, and/or alkyl
groups. Specific non-limiting examples include ethylene groups,
propylene groups, acrylonitrile groups, and/or methyl methacrylate
groups. In still another and/or alternative embodiment of the
present invention, the general formula of the polymer and/or
copolymer that can be used is set forth in the following
formula:
Hydrophobic Group.paren close-st..sub.xHydrophilic
Group).sub.y.sub.n
[0036] wherein x is the number of hydrophobic monomer units, y is
the number of hydrophilic monomer units, and n is the total number
of all monomer units in the polymer and/or copolymer chain. The x
and y values can stay constant or vary throughout the polymer
and/or copolymer chain. In addition, the type of hydrophobic
monomer or hydrophilic monomer can stay constant or vary throughout
the polymer and/or copolymer chain. Biological agents that form
anionic or cationic salts generally bond with the hydrophilic
groups in the polymer and/or copolymer chain. Consequently, the
more hydrophilic groups in the polymer and/or copolymer chain, the
higher the concentration of biological agents that can bond with
the polymer and/or copolymer chain. As can be appreciated, one or
more biological agents may bond with hydrophobic groups. Therefore,
the more hydrophobic groups in the polymer and/or copolymer chain,
the higher the concentration of biological agent that can bond with
the polymer and/or copolymer chain. Irrespective of whether a
biological agent bonds with a hydrophobic group or hydrophilic
group, the ratio of the hydrophilic groups to the hydrophobic
groups in the polymer and/or copolymer determines the amount of
biological agent that bonds with the polymer and/or copolymer. The
number of groups of hydrophilic groups (y) and hydrophobic groups
(x) typically varies from about 50 to over 10,000. Non-limiting
examples of polymer and/or copolymers that can be used include
poly(ethylene terephthalate); polyacetal; poly(lactic acid);
polyglycolic acid; polyesters; hydrogels; polytetrafluoroethylene;
fluorosilicones hyaluronates; polymethylmethacrylate; poly(ethylene
oxide)/poly(butylene terephthalate) copolymer; polycaprolactone;
poly(lactide-co-glycolide); poly(hydroxybutyrate);
poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester;
polyanhydride; poly(glycolic acid); copolymers of lactic acid and
glycolic acid; poly (caprolactone); poly (valerolactone); poly
(anhydrides); copolymers of poly (caprolactone) or poly (lactic
acid) with polyethylene glycol; poly(glycolic acid-co-trimethylene
carbonate); polyphosphoester; polyphosphoester urethane; poly(amino
acids); cyanoacrylates; poly(trimethylene carbonate); polyvinyl
alcohol; polyethylene; poly(iminocarbonate); polyorthoesters;
polyacetals; polyorthocarbonates; copoly(ether-esters) (e.g.
PEO/PLA); polyalkylene oxalates; polyphosphazenes; parylene;
biomolecules such as fibrin, fibrinogen, cellulose, starch,
collagen and hyaluronic acid; silicones; polyolefins;
polyisobutylene and ethylene-alphaolefin copolymers; acrylic
polymers and copolymers (e.g., n-butyl-acrylate, n-butyl
methacrylate, 2-ethylhexyl acrylate, lauryl-acrylate,
2-hydroxy-propyl acrylate); vinyl halide polymers and copolymers
(e.g. polyvinyl chloride); polyvinyl ethers (e.g. polyvinyl methyl
ether); polyvinylidene halides (e.g. polyvinylidene fluoride,
polyvinylidene chloride); polyacrylonitrile; polyvinyl ketones;
polyvinyl aromatics (e.g. polystyrene); polyvinyl esters (e.g.
polyvinyl acetate); copolymers of vinyl monomers; olefins (e.g.
ethylene-methyl methacrylate copolymers); acrylonitrile-styrene
copolymers; ABS resins; ethylene-vinyl acetate copolymers;
polyamides (e.g. Nylon 66, polycaprolactam); alkyd resins;
polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxy
resins; polyurethanes; rayon; rayon-triacetate; albumin; gelatin;
starch; dextrans; polysaccharides; fibrinogen; poly
(hydroxybutyrate); poly (alkylcarbonate); poly (orthoesters); EVA
copolymers; silicone rubber; poly (methylmethacrylate); cellulose
acetate; cellulose butyrate;
[0037] cellulose acetate butyrate; cellophane; cellulose nitrate;
cellulose propionate; cellulose ethers; and/or carboxymethyl
cellulose. One particular non-limiting copolymer chain that can be
used to form a polymer salt complex with a biological agent such
as, but not limited to, Trapidil, is an ethylene-acrylic acid
copolymer. In this copolymer, ethylene is the hydrophobic group and
acrylic acid is the hydrophilic group. The mole ratio of the
ethylene to the acrylic acid in the copolymer determines the
hydrophobicity of the copolymer. Generally a mole ratio for
hydrophobic groups/hydrophilic groups ranges from about 90:10-2:98;
however, other mole ratios can be used. As can be appreciated, a
mole ratio of 2:98 forms a hydrophilic copolymer and a mole ratio
of 90:10 forms a hydrophobic copolymer. In still another and/or
alternative embodiment of the present invention, the polymer and/or
copolymer includes parylene and/or derivatives thereof. Parylene is
substantially biologically inert, and forms a bond with many types
of biological agents such as, but not limited to Trapidil. The bond
between parylene is strong enough to retain the biological agent to
the parylene during the insertion of the stent into a body
passageway; however, the bond is weak enough to enable the bonded
biological agent to disengage from the parylene while in the body
passageway. The polyamide, parylene or parylene derivative can be
applied by catalyst-free vapor deposition to a coating thickness of
about 5,000 to 250,000 .ANG., which is adequate to provide a
controlled release of the Trapidil, and/or other biological agent.
"Parylene" is both a generic name for a known group of polymers
based on p-xylylene and can made by vapor phase polymerization.
More particularly, parylene or a parylene derivative can be created
by first heating p-xylene or a suitable derivative at an
appropriate temperature (e.g., about 950.degree. C.) to produce the
cyclic dimer di-p-xylylene (or a derivative thereof). The resultant
solid can be separated in pure form, and then cracked and pyrolyzed
at an appropriate temperature (e.g., about 680.degree. C.) to
produce a monomer vapor of p-xylylene (or derivative); the monomer
vapor is cooled to a suitable temperature (e.g., below about
50.degree. C.) and allowed to condense on the desired object (e.g.,
stent). The resultant polymer has the repeating structure
(CH.sub.2C.sub.6H.sub.4CH.sub.2).sub.n, with n equal to about
100-10,000, and a molecular weight in the range of about
100,000-1,000,000.
[0038] The parylene or parylene derivative is thought to form a
network resembling a fibrous mesh, with relatively large pores. As
more is deposited, the porous layer not only becomes thicker, but
it is believed that parylene or parylene derivative is also
deposited in the previously formed pores, making the existing pores
smaller. Careful and precise control over the deposition of the
parylene or parylene derivative therefore permits close control
over the release rate of the one or more biological agents. The
biological agent can be dispersed in the parylene or parylene
derivative, and/or the parylene or parylene derivative can be at
least partially coated over one or more layers of biological agent.
The porous layer also protects the biological agent during
deployment of the stent or other device during insertion of the
device through a catheter and into the vascular system or elsewhere
in the patient. In a further and/or alternative embodiment of the
invention, the polyamide, parylene or parylene derivative can be
applied by plasma deposition. Plasma is an ionized gas maintained
under vacuum and excited by electrical energy, typically in the
radiofrequency range. Because the gas is maintained under vacuum,
the plasma deposition process can occur at or near room
temperature. Plasma can be used to deposit polymers such as
poly(ethylene oxide), poly(ethylene glycol), and poly(propylene
oxide), as well as polymers of silicone, methane,
tetrafluoroethylene (including TEFLON brand polymers),
tetramethyldisiloxane, and others.
[0039] In still a further another and/or alternative feature of the
present invention, the amount of biological agent that can be
loaded on the polymer and/or copolymer is dependent on the
structure of the polymer and/or copolymer. For biological agents
that are cationic, the concentration of biological agent that can
be loaded on the polymer and/or copolymer is a function of the
concentration of anionic groups in the polymer and/or copolymer.
Alternatively, for biological agents that are anionic, the
concentration of biological agent that can be loaded on the polymer
and/or copolymer is a function of the concentration of cationic
groups (e.g. amine groups and the like) in the polymer and/or
copolymer. For instance, when the biological agent is such as, but
not limited to, Trapidil, the maximum concentration of Trapidil
that can be loaded on to the polymer and/or copolymer is dependent
on the concentration of anionic groups (i.e. carboxylate groups,
phosphate groups, sulfate groups, and/or other organic anionic
groups) in the polymer and/or copolymer, and the fraction of these
anionic groups that can ionically bind the cationic form of
Trapidil. As a result, the concentration of biological agent bound
to the polymer and/or copolymer can be varied by controlling the
amount of hydrophobic and hydrophilic monomer in the polymer and/or
copolymer, by controlling the efficiency of salt formation between
the biological agent, and/or the anionic/cationic groups in the
polymer and/or copolymer. Loading levels of the biological agent in
the polymer and/or copolymer can be from zero to about 90 percent
on a weight by weight basis. Therefore, the chemical properties of
the biological agent typically dictate the type of polymer and/or
copolymer to be used so as to deliver the desired levels of
biological agent into a body passageway to achieve a desired
biological response.
[0040] Yet a further another and/or alternative feature of the
present invention is that the stent is at least partially coated
and/or impregnated with one or more intermediate compounds that
include one or more biological agents, wherein the one or more
intermediate compounds are cross-linked to alter the rate of
release of the one or more biological agents into the body
passageway. It has been discovered that by causing the one or more
intermediate compounds to cross-link after being at least partially
coated and/or impregnated onto the stent, the rate at which the one
or more biological agents disassociates from the stent and migrates
into the body passageway can be controlled. As can be appreciated,
the cross-linking of the intermediate compound can be used to alter
the rate of release of the one or more biological agents into the
body passageway or other body parts. The cross-linking can be
instituted by a number to techniques including, but not limited to,
using catalysts, using radiation, using heat, and/or the like. In
one embodiment of the present invention, the intermediate compound
is exposed to radiation to cause one or more cross-links to be
formed. The radiation can include, but is not limited to, gamma
radiation, beta radiation and/or e-beam radiation. When the
intermediate compound is exposed to radiation, one or more hydrogen
radicals are removed from the polymer and/or copolymer chain in the
intermediate compound. The removal of the hydrogen radical causes
the polymer and/or copolymer chain to cross-link with another
portion of the polymer and/or copolymer chain or cross-link with a
different polymer and/or copolymer. The cross-linking effect
results in the one or more biological agents to become partially or
fully entrapped within the cross-linked intermediate compound. The
entrapped biological agent takes longer to release itself from the
cross-linked intermediate compound and to pass into the body
passageway. As a result, the amount of biological agent, and/or the
rate at which the biological agent is released from the stent over
time can be controlled by the amount of cross-linking in the
intermediate compound. The amount of cross-linking in the
intermediate compound is at least partially controlled by the type
and amount of radiation applied to the intermediate compound. Gamma
radiation is a higher intensity radiation and e-beam radiation is a
lower intensity radiation. Increased radiation intensities and
increased radiation exposure periods typically result in increased
cross-linking of the intermediate compound. Each polymer
composition has its unique threshold and capacity for
cross-linking. The amount of cross-linking that is induced by
radiation will be dependent on the chemical structure and
composition of the polymer and/or copolymer. The extent or degree
of cross-linking for each polymer and/or copolymer in combination
with the biological agent will vary, depending on the type,
strength and duration of radiation, the chemical structure of the
biological agent, the type of polymer and/or copolymer, and the
amount of loading (weight percent) of the biological agent in the
polymer and/or copolymer. Reduced solubility of the
copolymer/polymer in a body passageway can reduce the need for
induced cross-linking of the polymer and/or copolymer. For
instance, while the polymer and/or copolymer may be hydrophilic,
salt formation with a hydrophobic biological agent can result in a
reduction of solubility of the bound polymer and/or copolymer in
physiological environments. The reduction in solubility of the
bound polymer and/or copolymer may reduce the need or totally
obviate the need for induced cross-linking by radiation or
otherwise. The hydrophobic nature of the bound polymer and/or
copolymer will control the rate of release of the biological agent
from the polymer and/or copolymer. The amount of radiation exposure
to the intermediate compound and the biological agent is limited so
as to prevent degradation of the biological agent, and/or the
intermediate compound during the irradiation procedure. Generally,
less than about 2000 rads (irradiation absorbed doses) are applied
to the intermediate compound, the biological agent, and typically
less than about 1000 rads, and more typically less than about 500
rads, and even more typically less than about 400 rads. Generally,
at least about 0.1 rad is applied to the intermediate compound, the
biological agent, and typically at least about 1 rad, and more
typically at least about 10 rads. Alternatively, up to 300
microvolt equivalents is used.
[0041] A further another and/or alternative feature of the present
invention is that the stent is at least partially coated and/or
impregnated with one or more intermediate compounds that include
one or more biological agents, wherein the one or more intermediate
compounds are bonded with one or more biological agents to alter
the rate of release of the one or more biological agents into the
body passageway. It has been discovered that by causing the one or
more intermediate compounds to form a bond with one or more
biological agents after being at least partially coated and/or
impregnated onto the stent, the rate at which the one or more
biological agents disassociates from the stent and migrates into
the body passageway can be controlled. As can be appreciated, the
bonding of the one or more biological agents can be used to alter
the rate of release of the one or more biological agents into the
body passageway. The post bonding of the one or more biological
agents to one or more intermediate compounds can be instituted by a
number to techniques including, but not limited to, using
catalysts, using radiation, using heat, and/or the like. In one
embodiment of the present invention, the coating compound is
exposed to radiation to cause one or more bonds to be formed. The
radiation can include, but is not limited to, gamma radiation, beta
radiation and/or e-beam radiation. When the intermediate compound
is exposed to radiation, one or more hydrogen radicals are removed
from the polymer and/or copolymer chain in the intermediate
compound. The removal of the hydrogen radical causes the polymer
and/or copolymer chain to bond to one or more surrounding
biological agents. The hydrogen radical typically bonds with a salt
of the biological agents. The bonded biological agent takes longer
to release itself from the intermediate compound and to pass into
the body passageway. As a result, the amount of biological agent,
and/or the rate at which the biological agent is released from the
stent over time can be controlled by the amount of bonding of the
biological compound to the intermediate compound. The amount of
bonding of the biological compound to the intermediate compound is
at least partially controlled by the type and amount of radiation
applied to the intermediate compound. Increased radiation
intensities and increased radiation exposure periods typically
result in increased amounts of bonding. Each polymer composition
has its unique threshold and capacity for bonding with one or more
biological agents. The amount of bonding that is induced by
radiation will be dependent on the chemical structure and
composition of the polymer and/or copolymer and the biological
agents. The extent or degree of bonding for each polymer and/or
copolymer in combination with the biological agent will vary,
depending on the type, strength and duration of radiation, the
chemical structure of the biological agent, the type of polymer
and/or copolymer, and the amount of loading (weight percent) of the
biological agent in the polymer and/or copolymer.
[0042] Still yet a further another and/or alternative feature of
the present invention is that the stent is at least partially
sterilized by subjecting the stent to radiation. Prior to the
stent-being inserted into a body passageway, the stent should be
free or substantially free of foreign organisms so as to avoid
infection in the body passageway. In the past, the stent was
sterilized by ethylene oxide. Although this compound effectively
sterilized the stent, the FDA has imposed various restrictions on
this compound making it less desirable to use. Stent sterilization
by radiation overcomes the problems and limitations associated with
the use of ethylene oxide. The radiation destroys most, if not all,
of the foreign organisms on the stent. As a result, sterilization
by radiation reduces the occurrence of infection by foreign
organisms as compared to past sterilization techniques. Generally,
less than about 5000 rads (irradiation absorbed doses) are applied
to the stent to at least partially sterilize the stent, and
typically less than about 1000 rads, and more typically less than
about 500 rads. Generally, at least about 0.1 rad is applied to the
stent, and typically at least about 1 rad, and more typically at
least about 5 rads.
[0043] The primary object of the present invention is the provision
of a stent having improved procedural success rates.
[0044] Another and/or alternative object of the present invention
is the provision of a stent having higher visibility under
fluoroscopy in vivo.
[0045] Still another and/or alternative object of the present
invention is the provision of a stent retaining its longitudinal
dimensions from its original pre-expanded configuration to its
expanded configuration.
[0046] Yet another and/or alternative object of the present
invention is the provision of a stent that minimizes damage to
tissue during insertion and expansion of the stent.
[0047] Still yet another and/or alternative object of the present
invention is the provision of a stent that inhibits or prevents the
occurrence of in-stent restenosis, vascular narrowing and/or
restenosis long after the stent has been inserted into a body
passageway.
[0048] A further and/or alternative object of the present invention
is the provision of a stent that is simple and cost effective to
manufacture.
[0049] Still a further and/or alternative object of the present
invention is the provision of a stent that is at least partially
coated and/or impregnated with a biocompatible coating.
[0050] Yet a further and/or alternative object of the present
invention is the provision of a stent that includes two or more
body members connected by one or more connectors to allow
transverse bending and flexibility of the stent invariant to the
plane of bend.
[0051] Still yet a further and/or alternative object of the present
invention is the provision of a stent that is at least partially
visible under fluoroscopy in vivo.
[0052] Another and/or alternative object of the present invention
is the provision of a stent that is coated and/or impregnated with
one or more vascular active agents and/or secondary vascular
agents.
[0053] Still another and/or alternative object of the present
invention is the provision of a stent having one or more
intermediate compounds used with one or more vascular active agents
and/or secondary vascular agents to coat and/or impregnate one or
more vascular active agents and/or secondary vascular agents on the
stent.
[0054] Yet another and/or alternative object of the present
invention is the provision of a stent that is coated and/or
impregnated with one or more biological agents.
[0055] Still yet another and/or alternative object of the present
invention is the provision of a stent having one or more
intermediate compounds used with one or more biological agents to
coat and/or impregnate one or more biological agents on the
stent.
[0056] A further and/or alternative object of the present invention
is the provision of a stent having one or more intermediate
compounds to at least partially regulate or control the release of
one or more biological agents from the stent.
[0057] Still a further and/or alternative object of the present
invention is the provision of a stent having one or more
intermediate compounds that bond with one or more biological
agents.
[0058] Yet a further and/or alternative object of the present
invention is the provision of a stent having one or more
intermediate compounds that include polymers and/or copolymers
which include hydrophobic groups and hydrophilic groups.
[0059] Still yet a further and/or alternative object of the present
invention is the provision of a stent having one or more
intermediate compounds having post induced cross-linking to at
least partially regulate or control the release of one or more
biological agents from the stent.
[0060] Another and/or alternative object of the present invention
is the provision of a stent having one or more intermediate
compounds having post bonding with one or more biological agents to
at least partially regulate or control the release of one or more
biological agents from the stent.
[0061] Still another and/or alternative object of the present
invention is the provision of a stent having one or more
intermediate compounds that are subjected to radiation to cause
post induced cross-linking between the one or more intermediate
compounds and/or to cause post induced bonding with one or more
biological agents.
[0062] Yet another and/or alternative object of the present
invention is the provision of a stent that is sterilized prior to
insertion into a body passageway.
[0063] These and other advantages will become apparent to those
skilled in the art upon the reading and following of this
description taken together with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0064] Reference may now be made to the drawings, which illustrate
various embodiments that the invention may take in physical form
and in certain parts and arrangements of parts wherein:
[0065] FIG. 1 is a perspective view of a section of an unexpanded
stent which permits delivery of the stent into a body
passageway;
[0066] FIG. 1A is an enlarged perspective view of one end of the
stent of FIG. 1;
[0067] FIG. 2 is a perspective view of a section of the unexpanded
stent of FIG. 1 in a non-tubular state;
[0068] FIG. 3 is a sectional view of the unexpanded stent of FIG. 2
showing a connector used to connect the ends of two tubular body
members of the stent;
[0069] FIG. 3B is a perspective view of the stent of FIG. 1 in a
non-tubular state wherein the stent has rounded edges;
[0070] FIG. 4 is a sectional view of the stent of FIG. 2 showing
the polygonal structure of the stent before and after
expansion;
[0071] FIG. 5 is a perspective view of an additional embodiment of
the present invention showing an unexpanded section of the stent
having a series of slots of FIG. 4;
[0072] FIG. 6 is a sectional view of the stent of FIG. 5 showing a
connector used to connect the ends of two body members of the stent
together;
[0073] FIG. 7 is a sectional view of the stent of FIG. 5 showing a
part of the structure of the stent before and after expansion;
[0074] FIG. 8 is a perspective view of a stent of FIG. 1 showing a
coating that includes a biological agent on the stent;
[0075] FIG. 9 is a perspective view of an angioplasty balloon
delivering fluid materials to a local site;
[0076] FIG. 10 is a graphical representation of the steps for
coating the stent with a biological agent and coating compound;
[0077] FIG. 10A is a graphical representation of the biological
agent entrapped in a cross-linked polymer and/or copolymer; and,
FIG. 11 is a graphical representation of the steps to form
cross-linking of a polymer and/or copolymer that includes a
biological agent.
DETAILED DESCRIPTION OF THE INVENTION
[0078] Referring now to the drawings wherein the showing is for the
purpose of illustrating preferred embodiments of the invention only
and not for the purpose of limiting the same, FIGS. 1-8 disclose a
stent for a body passageway. The apparatus and structures of the
present invention may be utilized not only in connection with an
expandable stent for at least partially expanding occluded segments
of a body passageway, but also for additional uses. For example,
the expandable stent may be used for, but not limited to, such
purposes as 1) a supportive stent placement within a blocked
vasculature opened by transluminal recanalization, which are likely
to collapse in the absence of an internal support; 2) forming a
catheter passage through mediastinal and/or other veins occluded by
inoperable cancers; 3) reinforcement of catheter created
intrahepatic communications between portal and/or hepatic veins in
patients suffering from portal hypertension; 4) supportive stent
placement of narrowing of the esophagus, the intestine, the ureter
and/or the urethra; and/or 5) supportive stent reinforcement of
reopened and previously obstructed bile ducts. Accordingly, use of
the term "stent" encompasses the foregoing usages within various
types of body passageways, and also encompasses use for expanding a
body passageway.
[0079] The expandable stent 20, as shown in FIGS. 1, 1A, 2, 3, 3B,
and 4, generally comprises two tubular shaped body members 30,40,
each having a first end 32, 42, a second end 34, 44, and a wall
surface 36, 46 disposed between the first and second ends. The wall
surface is formed by a plurality of intersecting elongated members
50, with at least some of the elongated members intersecting with
one another intermediate the first and second ends of each body
member. As can be appreciated, the stent can be formed of only one
body member or be formed by more than two body members. Body
members 30,40 each have a first diameter which permits delivery of
the body members into a body passageway. As shown in FIG. 1, the
two body members have substantially the same first diameter. In
addition, FIG. 1 discloses that the first diameter of each body
member is substantially constant along the longitudinal length of
the two body members. As can be appreciated, the diameter of the
two body members can differ, and in addition or alternatively, one
or both of the body members can have a varying first diameter along
at least a portion of the longitudinal length of the body member.
Body members 30, 40 each have a second expanded diameter. The
second diameter typically varies in size; however, the second
diameter can be non-variable in size.
[0080] Elongated members 50, which form wall surface 36, 46 of body
members 30,40, can be any suitable material which is compatible
with the human body and the bodily fluids with which the stent may
come into contact. Typically, the elongated members are made of a
material, include a material, and/or are coated with a material
readily visible in vivo under fluoroscopic view. The elongated
members also are made of a material which has the requisite
strength and elasticity characteristics to permit the body members
to be expanded from their original cross-sectional size to their
expanded cross-sectional size and to further permit the body
members to retain their expanded configuration with the enlarged
cross-sectional size. Suitable materials for the fabrication of the
body members of the stent include, but are not limited to,
collagen, gold; platinum; platinum-iridium alloy; alloys of cobalt,
nickel, chromium and molybdenum; stainless steel; tantalum;
titanium; nickel-titanium alloy; magnesium, MP35N, MP20N, or
combinations of alloys; and/or any suitable polymer and/or
copolymer material (e.g. poly(L-lactide), poly(D,L-lactide),
poly(glycolide), poly(L-lactide-co-D,L-lactide),
poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide),
poly(glycolide-co-trimethylene carbonate), polydioxanone,
polyethylene oxide, polycaprolactone, polyhydroxybutyrate,
poly(phosphazene), poly(D,L-lactide-co-caprolactone)- ,
poly(glycolide-co-caprolactone, poly(phosphate ester),
polyanhydrides, poly(ortho esters), poly(phoshate ester),
poly(amino acid), polyacrylate, polyacrylamid, poly(hydroxyethyl
methacrylate), elastin polypeptide co-polymer, polyurethane,
polysiloxane and their copolymers) having the requisite
characteristics previously described. Typically, the one or more
body members are primarily made of stainless steel.
[0081] Elongated members 50 are generally small diameter wires or
bars that have a maximum cross-sectional length or diameter of up
to about 0.02 inches, and generally about 0.0005 to 0.008 inch, and
typically about 0.002 to 0.004 inch; however, other cross-sectional
lengths or diameters can be used. The cross-sectional length or
diameter of the elongated members is designated by "a" in FIG. 2.
It should, of course, be understood that each elongated member can
have a variety of different cross-sectional configurations along
part, or the complete length of, each elongated member. Such
configurations include circular, oval, elliptical, diamond,
triangular, trapezoidal, polygonal (e.g. square, rectangular,
hexagonal, etc.). In addition, the cross-sectional length or
diameter of the elongated members can be the same or different.
[0082] Referring to FIGS. 1, 2, 3B, and 4, the elongated members on
body members 30, 40 are arranged so as to form a plurality of
polygonal shapes such as, but not limited to parallelogram shapes
80, 90. The parallelogram pattern is such that similarly oriented
parallelograms are aligned on substantially the same longitudinal
axis of the body member. This pattern is best shown in FIGS. 2 and
3B. Referring now to FIG. 2, each parallelogram 80, 90 is formed by
four sides 82a, 82b, 82c, 82d, 92a, 92b, 92c, 92d. As shown in FIG.
2, a set of parallelogram shapes are aligned along a single
longitudinal axis of body member 30 which are defined by sides
82a-d, sides 82a of each parallelogram of body member 30
substantially lie in a single longitudinal axis. Likewise, sides
82c of each parallelogram of body member 30 substantially lie in a
single longitudinal axis. In addition, sides 82a and 82c of each
parallelogram are substantially parallel to each other. Sides 82b
and 82d of each parallelogram are substantially parallel to one
another. Sides 82b and 82d are shown to slope from left to right.
The slope angle between sides 82b and 82c and sides 82a and 82d
ranges between 0-90.degree., and typically about 10-60.degree.. The
parallelogram shape has a height "b." Height b will vary depending
or the size of the unexpanded body member. The maximum of height b
is about 1 inch, and generally about 0.005 to 0.5 inch, and
typically about 0.01 to 0.1 inch; however, other heights can be
used. Sides 82a and 82c can have the same or different length from
sides 82b and 82d . The length of the sides can be up to 2 inches,
and generally ranges from 0.005 to 1 inch, and typically 0.01 to
0.5 inch. As shown in FIG. 2, all the sides have substantially the
same length. Each of the parallelograms has substantially the same
dimensions.
[0083] Referring now to a set of parallelogram shapes aligned along
a longitudinal axis of body member 30 which are defined by sides
82a'-d', sides 82a' of each parallelogram of body member 30
substantially lie in a single longitudinal axis. Likewise, sides
82c' of each parallelogram of body member 30 substantially lie in a
single longitudinal axis. In addition, sides 82a' and 82c' of each
parallelogram are substantially parallel to each other. Sides 82b'
and 82d' of each parallelogram are substantially parallel to one
another. Sides 82b' and 82d' are shown to slope from right to left.
The slope angle between sides 82b' and 82c' and sides 82a' and 82d'
ranges between 0-90.degree., and typically about 10-60.degree.. The
parallelogram shape has a height "b'." Height b' will vary
depending or the size of the unexpanded body member. The height
ranges of b' are generally the same as b. The length ranges of
sides 82a-d are also generally the same as 82a'-d'.
[0084] As shown in FIG. 2, all the sides have substantially the
same length. Each of the parallelograms has substantially the same
dimensions. In addition, the shape and size of the parallelograms
is substantially the same as the parallelogram defined by sides
82a-d. Referring again to FIG. 2, the orientation of the
parallelograms alternates along the latitudinal axis from
parallelograms having sides 82b and 82d sloping from left to right
and parallelograms having sides 82b' and 82d' sloping from right to
left. A similar parallelogram pattern exists on body member 40.
Referring now to FIGS. 2 and 3B, the orientation of the
parallelograms that are aligned along the same longitudinal axis
for body members 30 and 40 is substantially the same. As can be
appreciated, this parallelogram pattern allows the body members to
be expanded without the body members having a reduction in length
in the longitudinal direction. Since a parallelogram is a four
sided figure with opposite sides. being parallel, the longitudinal
axis of structure of body members 30, 40 remains substantially the
same during the expansion of the body members. As can be
appreciated, the orientation of the parallelograms on one or more
body members of the stent can be patterned differently so long as
the longitudinal length of the body member remains substantially
the same during the expansion of the body member. The symmetrical
orientation of the parallelogram pattern on the body members
illustrated in FIGS. 1, 2, and 3B results in more uniform expansion
of the stent when in the body passageway. In one specific design of
a stent to be used in a blood vessel, the cross-sectional length or
diameter of the elongated members are substantially uniform and
about 0.0025 to 0.0035 inch, the size of the parallelograms in the
two body members are substantially the same, the heights b and b'
of the parallelograms are substantially the same and are about
0.015 to 0.025 inch, the lengths of the sides of each parallelogram
are substantially the same and are about 0.03 to 0.08 inch, and the
slope angles of the sides of the parallelograms are about
15-40.degree..
[0085] To provide flexibility to the stent, body members 30, 40 are
connected together by a several connector members 70. One such
connector member is a connector member having a "U" shaped member
72 as shown in FIGS. 1, 2 and 3. As best shown in FIGS. 1 and 2,
connector member 70 joins end 34 of body member 30 to end 42 of
body member 40. Four connector members are shown to connect the two
body members together. Connector member 70 also includes a bar
member 74. The bar member spans between the second end of "U"
shaped member 72 and end 42 of body member 40. The first end of "U"
shaped member 72 is connected to end 34 of body member 30. As best
shown in FIG. 2, connectors 70 do not connect to all of the ends 34
of body member 30 or all of the ends 42 of body member 40.
[0086] Referring to FIG. 3, the connector member has certain
dimensions that enhance the flexibility of the stent. The
cross-sectional length or diameter of the "U" shaped member is
generally the same as the cross-sectional length or diameter "a" of
the elongated members; however, other cross-sectional lengths or
diameters of the "U" shaped member can be used. The height of the
legs of the "U" shaped member is generally equal to 2a+(b or b')
wherein "a" is the cross-sectional length or diameter of the
elongated members and b or b' is the height of the parallelograms
in the unexpanded state. As can be appreciated, other heights of
the legs of the "U" shaped member can be used. The width "c" of the
"U" shaped member also affects the flexibility of the connector
member and the stent. The width generally is about 1-4 times the
cross-sectional length or diameter "a" of the "U" shaped member,
and typically about 1.2-2 times the cross-sectional length or
diameter "a" of the "U" shaped member; however, other widths can be
used. In addition, the spacing of the "U" shaped member from ends
34 of body member 30 and end 42 of body member 40 also affects the
flexibility of the connector member and the stent. As shown in FIG.
2, the "U" shaped portion of the connector member is spaced a
distance from the ends of the body members that is substantially
equal to cross-sectional length or diameter "a" of the elongated
members. Bar member 74 has a sufficient length to form the desired
spacing of the "U" shaped portion of the connector member from ends
of body member 40. The connector member allows the body members to
transverse, bend and improve flexibility invariant to the plane of
bending. As can be appreciated, other shaped connectors which
include an arcuate portion and/or V-shaped portion can be used.
[0087] Referring now to FIG. 1A, ends 32, 34, 42, and 44 are
treated so as to have generally smooth surfaces 60. Generally, the
ends are treated by filing, buffing, polishing, grinding, and/or
the like the end surfaces. As a result, sharp edges, pointed
surfaces and the like are substantially eliminated from the end
section. Typically all the ends of the body members are treated to
have smooth surfaces. The smooth surfaces of the ends reduce damage
to surrounding tissue as the body member is positioned in and/or
expanded in a body passageway. In addition to the ends having
generally smooth surfaces, the elongated members 50 and/or joints
between the elongated members are formed, filed, buffed, ground,
polished, and/or the like to also have generally smooth surfaces.
Furthermore, connector members 70 and/or the connection points
between the connector members and the elongated members are formed,
filed, buffed, ground, polished, and/or the like to have generally
smooth surfaces. The substantial removal of sharp edges, pointed
surfaces and the like from the entire stent reduces damage to
surrounding tissue as the stent is positioned in and/or expanded in
a body passageway. As can be appreciated, the ends of the body
members, the elongated members, the joints between the elongated
members, the connector members, and/or the connection points
between the elongated members and the connector members can
additionally or alternatively be coated with a material that
reduces or eliminates any sharp and/or rough surfaces. The coating,
if used, is generally a polymer and/or copolymer material. The
coating can be nonbiodegradable, biodegradable or
semi-biodegradable. Typically the coating thickness is less than
the cross-sectional thickness of the elongated members. One
non-limiting example of a coating thickness is about 0.00005 to
0.0005 inches.
[0088] Elongated members 50 and/or connector members 70 can be
formed by a variety of processes. Typically, the elongated members
and connector members are formed by etching, laser cutting and/or
punching a single piece of material so that the individual
intersections of the elongated members and/or the connections
between the elongated members and the connector members need not be
welded, soldered, glued or otherwise connected together. For
example, the stent can be formed from a thin-walled metal tube, and
the openings between the elongated members and the connector
members are formed by an etching process, such as electromechanical
or laser etching, whereby the resultant structure is a stent having
a plurality of intersecting elongated members and connector members
as shown in FIG. 1. This technique enhances the structural
integrity of the structure and reduces the number of rough surfaces
at the intersection points. An alternative method or process to
form the stent is to use a flat piece of material and form the
openings between the elongated members and the connector members by
an etching process, such as electromechanical or laser etching,
stamping, laser cutting, drilling, and/or the like. Such a flat
piece of material is illustrated in FIGS. 3 and 3B.
[0089] Referring specifically to FIG. 3B, the complete stent with
the cut out regions is shown prior to the stent being formed into a
tubular shape or some other cross-sectional shape. The flat sheet
includes seven (7) formed parallelograms along the latitudinal axis
of the sheet and one partially formed parallelogram. The flat sheet
also includes ten (10) parallelograms along the longitudinal axis
of the sheet. Four "U" shaped connector members are formed along
the latitudinal axis of the sheet. The connector members divide the
parallelograms along the longitudinal axis of the sheet into two
sets of five (5), thus each body member has five (5) parallelograms
along the longitudinal axis and seven (7) fully formed
parallelograms and one partially formed parallelogram along the
latitudinal axis. As shown in FIG. 3B, body members 30, 40 each
have an elongated top bar 38, 48. In addition, body members 30, 40
each have a plurality of ends 39, 49 formed from sides 82b', 82d',
92b', and 92d' that are not connected to sides 82c' and 92c',
respectively. When the flat sheet is formed into a tubular shape or
some other cross-sectional shape, ends 39, 49 are connected to top
bar 38, 48 thereby resulting in a fully formed parallelogram,
thereby resulting in eight (8) fully formed parallelograms about
the outer surface of body members 30, 40. Typically, the flat sheet
is designed so as to form an even number of fully formed
parallelograms about the outer surface of body members 30,40. This
even number of formed parallelograms facilitates in the desired
expansion of the stent in the body passageway. The connections
between ends 39, 49 and top bar 38, 48 can be formed by welding,
soldering, brazing, adhesives, lock and groove configurations, snap
configurations, melting together the ends and the top bars, and the
like. Typically, after the connection has been made, the surfaces
around the connection are smoothed to remove sharp and/or rough
surfaces. FIG. 3B illustrates ends 32,34,42, and 44 as being smooth
surfaces. Ends 39 are also shown as being relatively smooth
surfaces.
[0090] Referring now to FIG. 4, there is shown a single
parallelogram shape 80. The left parallelogram shape is
representative of the parallelogram shapes in body members 30,40
when the stent is in an unexpanded configuration. The length of the
sides of the parallelogram are illustrated as being generally the
same, thereby forming a rhombus. The angle between sides 82b and
82c and sides 82a and 82d is about 15-30.degree.. When the stent is
expanded, the parallelogram shape deforms thereby causing the angle
between sides 82b and 82c and sides 82a and 82d to increase. A
fully expanded stent would result in the angle between sides 82b
and 82c and sides 82a and 82d to be about 90.degree. thereby
causing the parallelogram to form into a square or rectangle.
Generally, the stent is not fully expanded, thus an angle of less
than 90.degree. is formed between sides 82b and 82c and sides 82a
and 82d. The right side dashed parallelogram illustrates the
typically expanded configuration of the parallelogram. In the
expanded state, the angle between sides 82bb and 82cc and sides
82aa and 82dd generally remain the same and generally range between
about 60-90.degree., and typically about 65-80.degree..
[0091] Referring now to FIGS. 5, 6, and 7, a second embodiment of
the present invention is illustrated. As shown in FIG. 5, a stent
100 includes two body members 110, 112. As can be appreciated,
stent 100 can include more than two body members. Body members 110,
112 include ends 140, 142 of body member 110 and ends 144, 146 of
body member 112. The two body members are connected together by
several connector members 120. Generally, connector members 120
include an arcuate shaped member 122, and typically is "U" shaped,
similar to shape and size of connector members 70 as shown in FIG.
3B. Connector member 120 also includes a bar member 124. The
connector members provide flexibility to the stent body members
110, 112. The bar member spans between the second end of "U" shaped
member 122 and end. As best shown in FIGS. 5 and 6, the "U" shaped
member alternates between being connected to end 142 and end 144
and similarly, the bar member alternates between being connected to
end 144 and end 142. The "U" shaped members are typically spaced
apart a sufficient distance so as to avoid contacting one another
in the unexpanded state. In addition, the "U" shaped members are
typically spaced apart a sufficient distance so as to avoid
contacting one another in the expanded state. The connector members
allow the body members to transverse, bend and improve flexibility
invariant to the plane of bending. As can be appreciated, other
shaped connectors which include an arcuate portion can be used.
[0092] Referring to FIG. 5, body members 110, 112 are substantially
symmetrical to one another and typically have substantially
identical dimensions. Each body member includes a plurality of
slots 130, 132. Slots 130, 132 are generally equal in length and
width; however, the width and/or length of the slots can vary. Each
slot 130 includes two ends 130a, 130b and each slot 132 includes
two ends 132a, 132b. Each series of slots 130 along a longitudinal
axis of the stent are arranged substantially parallel to one
another. Similarly, each series of slots 132 along a longitudinal
axis of the stent are arranged substantially parallel to one
another. Slots 130 and 132 that are positioned closest to one
another form a series of "V" shapes along a longitudinal axis of
the stent. Ends 130a and 132a form the base of the "V" shape. As
shown in FIG. 5, four different series of "V" shapes are positioned
along a longitudinal axis of the stent. As shown in FIG. 5, all the
"V" shapes are symmetrically oriented on each body member. The
angle between slots 130 and 132 is between about 0-90.degree., and
generally about 5-60.degree., and typically about 10-30.degree..
The width of each slot is up to about 0.5 inch, and generally about
0.0005 to 0.25 inch, and typically about 0.001 to 0.1 inch. The
length of each slots is up to about 2 inches, and generally about
0.005 to 1 inch, and typically about 0.01 to 0.5 inch. As can be
appreciated, the slot arrangement is such that the stent retains
its longitudinal length from its unexpanded to its expanded state.
The configuration of slots 130, 132 in the pre-expanded and
post-expanded position is shown in FIG. 7. The slot configuration
in the left figure illustrates the slots in the unexpanded state.
The slot configuration in the right figure illustrates the slots in
the expanded state. As illustrated in the expanded state, the slots
130 and 132 begin to align and the angle between the slots
increases. Generally, the angle between the slots in the expanded
state is between about 45-90.degree., and typically about
60-80.degree.. In one specific design of a stent to be used in a
blood vessel, four sets of "V" shaped slots are positioned in each
body member and eight connector members are used to connect the two
body members together. The length of all the slot members are
substantially the same. The angle between slots is about
15-25.degree. in the unexpanded state. The width of each slot is
about 0.002-0.007 inch. The length of each slot is 0.05-0.2
inch.
[0093] The slots in the body members can be formed in a variety of
manners. In one method or process, the stent is formed from a flat
piece of material and the slots and connector members are formed by
an etching process, such as electromechanical or laser etching,
stamping, laser cutting, drilling, and/or the like. After the slots
are formed, the stent is generally treated so as to have generally
smooth surfaces 60. Generally, the ends, slots and connector
members are treated by filing, buffing, polishing, grinding, and/or
the like. As a result, sharp edges, pointed surfaces and the like
are substantially eliminated. The smooth surfaces reduce damage to
surrounding tissue as the body member is positioned in and/or
expanded in a body passageway. As can be appreciated, the ends of
the body members, the slots, and/or the connector members can
additionally or alternatively be coated and/or impregnated with a
material that reduces or eliminates any sharp and/or rough
surfaces. The coating, if used, is generally a polymer and/or
copolymer material. The coating can be non-biodegradable,
biodegradable or semi-biodegradable. Typically the coating
thickness is less than the half the width of the slots. One
non-limiting example of a coating thickness is about 0.00005 to
0.0005 inches.
[0094] After the flat material has the slots and connector members
inserted therein, the flat material is rolled or otherwise formed
and the side edges of the flat material are connected together form
the stent. The side edges of the flat material can be connected
together by a variety of techniques such as, but not limited to,
welding, soldering, brazing, adhesives, lock and groove
configurations, snap configurations, melting together the edges,
and the like. The cross-sectional shape of the stent is typically
circular; however, other cross-sectional shapes can be formed such
as, but not limited to, oval, elliptical, diamond, triangular,
trapezoidal, polygonal (e.g. square, rectangular, hexagonal, etc.).
The connection between the edges is generally treated to reduce or
eliminate the rough or sharp surfaces.
[0095] Referring now to FIG. 8, a stent 200 is shown to include a
compound 210 on the elongated members 220 and connector 230 of the
body member. Compound 210 is or includes a vascular active agent
that inhibits and/or prevents restenosis, vascular narrowing and/or
in-stent restenosis. As can be appreciated, compound can
alternatively or also be a secondary vascular active agent and/or a
biological agent. As can be appreciated, compound 2 1 0 can
represent one or more different compounds. One preferable compound
that is or is included in the vascular active agent is a PDGF
inhibitor. One type of PDGF inhibitor that is used is Trapidil
and/or derivative thereof; however, other PDGF inhibitors can be
used. Another preferable compound that is or is included in the
vascular active agent is GM-CSF and/or derivative thereof.
[0096] The amount of vascular active agent and/or secondary
vascular active agent and/or other biological agent delivered to a
certain region of a body passageway can be controlled by varying
the coating thickness, drug concentration of the vascular active
agent and/or secondary vascular active agent and/or other
biological agent, the solubility of the vascular active agent
and/or secondary vascular active agent and/or other biological
agent in a particular body passageway, the amount of surface area
of the body member 200 that is coated and/or impregnated with the
vascular active agent and/or secondary vascular active agent and/or
other biological agent, the location of the vascular active agent
and/or secondary vascular active agent and/or other biological
agent on the stent, and/or the size of cavity openings in the
stent. As can be appreciated, the vascular active agent and/or
secondary vascular active agent and/or other biological agent can
be combined with, or at least partially coated with, another
compound that affects the rate at which the vascular active agent
and/or secondary vascular active agent and/or other biological
agent is released from the surface of the stent. An intermediate
compound can be used in conjunction with compound 210 to assist in
binding compound 210 to body member 200. In addition, or
alternatively, the intermediate compound can be used to control the
release of compound 210 into the body passageways. In one
particular application, the intermediate compound is biodegradable
and dissolves over the course of time, and the intermediate
compound is coated at one or more thicknesses over compound 210 to
delay delivery of compound 210 into a body passageway.
[0097] Referring now to FIGS. 10, 10A and 11, the vascular active
agent and/or secondary vascular active agent and/or other
biological agent is combined with a polymer and/or copolymer prior
to being at least partially coated onto the stent. The polymer
and/or copolymer can be formulated to bond the vascular active
agent and/or secondary vascular active agent and/or other
biological agent to the stent; however, the polymer and/or
copolymer can be used in combination with other compounds to
facilitate in the bonding of the vascular active agent, secondary
vascular active agent and/or other biological agent and/or polymer
and/or copolymer to the stent. Referring now to FIG. 10, there is
illustrated a typical process whereby one or more vascular active
agents, one or more secondary vascular active agents, one or more
other biological agents, and/or other compounds are coated to the
stent. As shown in FIG. 10, the vascular active agent and/or
secondary vascular active agent and/or other biological agent is
mixed with a polymer and/or copolymer prior to coating the stent.
The polymer and/or copolymer is formulated to delay and/or regulate
the time and/or amount of vascular active agent and/or secondary
vascular active agent and/or other biological agent being released
into the body passageway. The polymer and/or copolymer can be a
biodegradable compound, a non-biodegradable compound, or a
partially biodegradable compound. The polymer and/or copolymer can
be formulated so as to form one or more bonds with the vascular
active agent and/or secondary vascular active agent and/or other
biological agent, or be chemically inert with respect to the
vascular active agent and/or secondary vascular active agent and/or
other biological agent. Generally, the polymer and/or copolymer
form at least one bond with one or more vascular active agents
and/or secondary vascular active agents and/or other biological
agents. The bond is generally formed in a polymer and/or copolymer
salt complex. For example, when the vascular active agent is or
includes Trapidil, the Trapidil forms a salt complex with the
polymer and/or copolymer. The Trapidil forms the cationic component
of the salt complex and the polymer and/or copolymer forms the
anionic component of the salt complex. Typically, the carboxylate
groups, phosphate groups, and/or sulfate groups in the polymer
and/or copolymer form the bond with this vascular active agent.
[0098] After the vascular active agent and/or secondary vascular
active agent and/or other biological agent has been mixed with the
polymer and/or copolymer, the mixture is coated onto the stent.
After the stent or a portion of the stent has been coated with the
mixture, the coated stent can be subjected to radiation. The
radiation causes the polymer and/or copolymer to form cross-linking
between the polymer and/or copolymer chains and/or causes one or
more bonds to form between the polymer and/or copolymer and the
vascular active agent and/or secondary vascular active agent and/or
other biological agent. The cross-linking and/or bond formation
alters the rate of release of the one or more vascular active
agents and/or secondary vascular active agents and/or other
biological agents into the body passageway. The radiation typically
includes, but is not limited to, gamma radiation, beta radiation,
and/or e-beam radiation; however, other types of radiation (e.g.
inferred, ultraviolet) can be used in conjunction with or as an
alternative to gamma radiation, beta radiation, and/or e-beam
radiation. When the polymer and/or copolymer is exposed to
radiation, one or more hydrogen radicals are typically removed from
the polymer and/or copolymer chain. This process is illustrated in
FIG. 11. As can be appreciated, other elements in the polymer
and/or copolymer can be removed and/or disassociated from the
polymer and/or copolymer when the polymer and/or copolymer is
exposed to radiation.
[0099] As illustrated in FIG. 11, a polymer and/or copolymer chain
includes a carboxyl group that has formed a salt complex with
Trapidil. Radiation is applied to the polymer and/or copolymer salt
complex resulting in removal of one or more hydrogen atoms from the
polymer and/or copolymer chain. The removal of the hydrogen radical
causes the polymer and/or copolymer chain to cross-link with
another portion of the polymer and/or copolymer chain or cross-link
with a different polymer and/or copolymer as shown in FIG. 11. FIG.
10A illustrates the vascular active agent and/or secondary vascular
active agent and/or other biological agent being entrapped or
partially entrapped within the cross-linking of the polymer and/or
copolymer. The entrapped vascular active agent and/or secondary
vascular active agent and/or other biological agent takes longer to
release itself from the cross-linked coating compound and to pass
into the body passageway. As a result, the amount of vascular
active agent and/or secondary vascular active agent and/or other
biological agent, and/or rate at which the vascular active agent
and/or secondary vascular active agent and/or other biological
agent released from the stent over time can be controlled by the
amount of cross-linking in the coating compound and/or the amount
of bonding in the coating compound. The amount of cross-linking
and/or bonding in the coating compound is controlled by the type
and amount of radiation applied to the coating compound. The amount
of radiation exposure to the polymer and/or copolymer salt complex
is controlled so as to prevent degradation of the vascular active
agent, secondary vascular active agent, other biological agent,
and/or polymer and/or copolymer during the irradiation procedure.
In addition to the radiation causing cross-linking and/or bonding,
the radiation at least partially sterilizes the stent. The
radiation destroys most if not all of the foreign organisms on the
stent and/or on any coating on the stent. As a result,
sterilization by radiation reduces the occurrence of infection by
foreign organisms.
[0100] Referring now to FIG. 9, a vascular active agent and/or
secondary vascular active agent and/or other biological agent 240
is delivered into a body passageway A via angioplasty balloon 250.
Balloon 250 includes one or more slots 260 to allow delivery of
vascular active agent and/or secondary vascular active agent and/or
other biological agent 240 into body passageway A. Balloon 250 can
be used to both deliver compound 210 and expand the stent 200, or
be used in conjunction with another balloon or stent expanding
device. When the vascular active agent includes one or more PDGF
inhibitors, local delivery of the inhibitor by a stent and/or via a
balloon is highly advantageous.
[0101] The present invention has been described with reference to a
number of different embodiments. It is to be understood that the
invention is not limited to the exact details of construction,
operation, exact materials or embodiments shown and described, as
obvious modifications and equivalents will be apparent to one
skilled in the art. It is believed that many modifications and
alterations to the embodiments disclosed will readily suggest
themselves to those skilled in the art upon reading and
understanding the detailed description of the invention. It is
intended to include all such modifications and alterations insofar
as they come within the scope of the present invention.
* * * * *